#rmsd

[jhavelikes]

The RGD (Arg-Gly-Asp)-binding integrins αvβ6 and αvβ8 are clinically validated cancer and fibrosis targets of considerable therapeutic importance. Compounds that can discriminate between the two closely related integrin proteins and other RGD integrins, stabilize specific conformational states, and have sufficient stability enabling tissue restricted administration could have considerable therapeutic utility. Existing small molecules and antibody inhibitors do not have all of these properties, and hence there is a need for new approaches. Here we describe a method for computationally designing hyperstable RGD-containing miniproteins that are highly selective for a single RGD integrin heterodimer and conformational state, and use this strategy to design inhibitors of αvβ6 and αvβ8 with high selectivity. The αvβ6 and αvβ8 inhibitors have picomolar affinities for their targets, and >1000-fold selectivity over other RGD integrins. CryoEM structures are within 0.6-0.7Å root-mean-square deviation (RMSD) to the computational design models; the designed αvβ6 inhibitor and native ligand stabilize the open conformation in contrast to the therapeutic anti-αvβ6 antibody BG00011 that stabilizes the bent-closed conformation and caused on-target toxicity in patients with lung fibrosis, and the αvβ8 inhibitor maintains the constitutively fixed extended-closed αvβ8 conformation. In a mouse model of bleomycin-induced lung fibrosis, the αvβ6 inhibitor potently reduced fibrotic burden and improved overall lung mechanics when delivered via oropharyngeal administration mimicking inhalation, demonstrating the therapeutic potential of de novo designed integrin binding proteins with high selectivity.

De novo design of highly selective miniprotein inhibitors of integrins αvβ6 and αvβ8 | bioRxiv

[sbgridconsortium]

A look into specific interactions between Bruton’s Tyrosine Kinase (BTK) and its inhibitors

Note: This publication highlight is part of the SBGrid/Meharry Medical College Communities Project, focused on science education and demonstrating how structural biology and preclinical science connect to medicine.

Non-receptor tyrosine kinases (nRTK) are a subgroup of tyrosine kinases that are responsible for the phosphorylation of proteins. As the name suggests, tyrosine kinases work by transferring a phosphate group from ATP to the tyrosine residue of a protein. Non-receptor refers to the group of tyrosine kinases found within the cytosol of the cell, unlike receptor kinases, which are embedded into the cellular membrane. nRTKs are involved in many cell functions such as regulating cell growth and proliferation. They also play critical roles in immune system regulation. One specific nRTK that is involved in propagating signals from B cell receptors is known as Bruton’s tyrosine kinase (BTK). BTK’s importance was discovered when it was revealed that mutations in the Btk gene, the gene that encodes BTK, leads to the development of X-linked agammaglobulinemia (XLA), an immunodeficiency disease. BTK also plays essential roles in many diseases such as mantle cell lymphoma, chronic lymphocytic leukemia, Waldenstrom macroglobulinemia, small lymphocytic lymphoma, marginal zone lymphoma, and chronic graft-versus-host disease, just to name a few. These factors combined have made BTK inhibition a target of several drug therapies aimed at treating B cell malignancies. These therapies include the first in class BTK inhibitor, Ibrutinib, and the second-generation inhibitors Acalabrutinib, Zanubrutinib and Orelabrutinib. Although all of these therapeutics have seen success in clinical applications, specific interactions between the drugs and BTK are not well understood. 

Above: Front and back views of BTK/Acalabrutinib complex (PDB: 8FD9)  CC BY SBGRID.

In this work, SBGrid member Amy Andreotti and colleague David Lin reported the first structure of BTK in complex with Acalabrutinib. They also report a structure of BTK with Tirabrutinib, another second-gen BTK inhibitor that, at the time of this publication, is in clinical use in Japan and Taiwan but not yet FDA approved. When comparing their BTK/Acalabrutinib complex structure with a previously reported structure of BTK/Ibrutinib complex, the authors noted several regions where structural differences occur based on evaluation of RMSD values. Comparisons between BTK/Acalabrutinib and BTK/Tirabrutinib reveal large conformational differences in the activation loop that the authors attribute to the kinase undergoing dynamic fluctuations when bound to the drug, after further investigation of the previously reported structure of BTK/Tirabrutinib complex. Along with broad structure characterization, the authors also identified a few key residues that interact with the inhibitors. Combined, their work shows the need for further probing into how these drugs interact with BTK in order to fully examine how these inhibitors bind. 

Read more in PLOS One 

- KeAndreya Morrison, Meharry Medical College

[hideki0145]

中華ゲーム機RG35XXを購入してみた

所有欲を感じるクオリティの高い製品

前回このBlogを再開する理由として『技術分野の投稿や日常のなんでもない投稿に当てはまらない投稿はこちらで再開しようかな～』と挙げていましたが、それがこちら「中華ゲーム機」についての投稿でした。

今回購入したのはANBERNIC社の「RG35XX」です。日本語対応の公式サイトでも購入可能で、その場合は配送料は別となっています。

いざ開封

開封してみました。内容物を確認すると、

RG35XX本体

取扱説明書

画面保護フィルム一式

充電用USBケーブル(A to C)

となっています。付属の画面保護フィルムはガラスフィルムなので、非光沢のものが欲しければ別途購入して準備しておきましょう。 自分はTwitterでおすすめされていたPDA工房さんのものを貼り付けました。PDA工房さんは端末さえ貸し出しすればどんな端末の保護フィルムでも作成してくれるんですね〜、先人の方に感謝です！

ということで保護フィルムを貼り付けした本体はこちら！ 写真からは伝わりづらいかもしれませんが、製品のクオリティがとても高くて驚きました…！ プラスチック筐体ですが、変なバリが残っているとか隙間が空いているとか、そんな箇所は自分の端末には見られませんでした！

本体背面はこのような感じです。 小さい頃に憧れたクリア筐体、基板が透けて本当にカッコ良い！

こんなものも合わせて購入しました

本体に合わせて購入したのは、

ダイソー カメラプロテクトケース(ブラック)

バッファロー microSD 64GB RMSD-064U11HA/N

PDA工房 ANBERNIC RG35XX対応 PerfectShield

です。RG35XXの面白いところは、microSDカードにセットアップしたカスタムファームウェア(以後CFW)でブートできることです！ CFWはLinuxベースで、今回はGarlicOSというものをセットアップしたのですが…このCFWのクオリティにもとても驚かされています…！

GarlicOSの導入記事自体はググると沢山先人の方のものが見つかるのですが、「こんなツールを使用しても導入できるよ〜」という事例はいくらあっても構わないかと思うので次回セットアップ手順を紹介したいと思います。

それでは！

[rbesjournal]

In Silico Analyzes for the Inhibition of HIV Protease by Ritonavir and Indinavir

Introduction: This research was conducted to investigate the molecular interaction of HIV protease inhibitor drugs using molecular docking. HIV protease is responsible for processing gag and gag-polyproteins during virion maturation. The activity of this enzyme is essential against viral infections and has beneficial therapeutic effects on HIV treatment. Materials and Methods: To meet the aim of the study, indinavir and ritonavir were selected as HIV Protease inhibitor drugs. The necessary information on molecular docking was collected through information servers, such as Drug bank and Program database (PDB). Then, molecular docking was performed using Molegro virtual docker software. In order to check the stability of the resulting complex structure and its cellular penetration, a molecular dynamics simulation was run for 50 nanoseconds using GROMACS2019.6 package and Amber99SB force force field. During the molecular dynamics simulation, root mean square deviations (RMSD), root mean square fluctuations (RMSF), the radius of gyration (RG), hydrogen bonds, and distance between ligands and complex were investigated. Results: The obtained results indicated that the RMSD of the complex of the ligands and HIV protease at the end of 50 nanoseconds had a linear slope. Hydrogen bonds decreased at beginning of simulation but they increase at the end of simulation However RG was decreased at the end of the simulation Also the RMSF was decreased at the end of simulation rather than beginning of simulation, So all the obtained results showing the stability and strength of the structure. Conclusion: Molecular docking method can indicate the relationship between structure-activity and the effectiveness of ligands on HIV protease based on the level of interaction between the ligands and the receptors.

[akabrat]

Infusion day!!! Hopefully last time at an infusion center. Sounds like they are going to be shopping my meds directly to me. Hopefully everything goes well if not I enjoy having someone else poke me and around just in case.#infusionday #freedompump #rmsd https://www.instagram.com/p/B0ZQK3zg7Xp/?igshid=1asv1sjky79ur

[bansheecloud]

Dell Chromebook CB1C13-R2, REFURBISHED

Dell Chromebook CB1C13-R2, REFURBISHED

The Dell Chromebook CB1C13-R2 is designed for students, but its long battery life and compact, lightweight design make it great for general home use as well.

  Specifications:

Dell Chromebook CB1C13-R2, REFURBISHED

Processor: Intel® Celeron® Dual Core 2955U-1 @1.40Ghz

Hard Drive(s): 16G (eMMC)

Memory: 4G

Video Card: UMA

RMSD / Optical Drive: N/A

Power Supply (Internal or External): External

Power…

[davidrussellschilling]

Atomic Structure Advantages & Disadvantages

Atomic Structure Advantages & Disadvantages

C O N T E N T S:

KEY TOPICS

Currently, the major challenges in RNA structure prediction lie in (1) further improvement of algorithms that incorporate simple experimental data (contact-assisted data), (2) structure optimization to alleviate atomic clashes and improve accuracy, and (3) accumulation of comprehensive RNA structure knowledge with the help of database increases and automated structural…

[yasurin0622-blog]

お昼〜 ざる蕎麦 https://www.instagram.com/p/Cg5voz-rmSd/?igshid=NGJjMDIxMWI=

[sciencepunchman]

Problems of Structure Based Drug Design and Molecular Docking Softwares

The ultimate docking is to determine the binding probability of two molecules by calculating the geometric shape compatibility and molecular affinity with computer algorithms.

Protein-ligand or protein-protein interaction modelling softwares have been developed over years. Computers have become stronger, different algorithms are made, more complex functions implemented. All of these factors contributed to simulate a real life molecular interaction software. Unfortunately we haven’t achieved yet. 

For the sake of drug discovery, we’ve screened drug candidates and tried to find novel therapeutics in medicine and predict the outcome of the complex molecular interaction. It did give us valuable information but also gave false positive results.

The physiology of the docking software

Docking is all about posing and scoring. Posing means depicting molecular geometric compatibility in a 3D space whereas scoring is to calculate simulative reaction free energy and predicting the binding affinity of the molecules. Docking is more probable if the molecules are geometrically favorable, has negative free energy and high affinity.

The inputs of the docking software are 3D x-ray crystallography or nmr spectroscopy images of interacting molecules and the output is the score function result and final geometric shape.

Of course the crystal image is not how the molecule behaves or does not show its’ all possible configurations. One can say, the crystal image is the snapshot of the molecule.

Prediction of protonation in certain pH environments is one of the most important calculations that the computer must address.

The problems

Imperfect x-ray crystallography or nmr spectroscopy images.

Challenge to differentiate O, N or double bonded carbon atoms in crystallography.

Low density images

Xray structures don’t have information about protonation of O or N atoms.

The challenge of chemistry itself.

The 360 degree rotating nature of single C-C bonds

Tautomerism

Pseudorotation

Unsatisfied hydrogen bonds vs hydrophobicity

Protonation

Limitations of computers

Insufficient computer power to analyze all the conformational changes

Complexity of H2O-water molecules.

Q & A

How does a software deal with some of the problems of imperfect crystallography images, the nature of chemistry and the limitations of computer power?

> You can use prediction tools for most of the situations including rotations, tautomers, protonations, side chain flips or water orientations.

> Crystallography problems might be solved by using multiple crystal structure if available.

> For torsional and rotational problems, you can split the molecule into pieces and try to fit into the pocket. First, the base portion docking construction is optimized and several possible solution are made. The next step is docking the 2nd part of the molecule. Again, several variations are made, but the variations should be continuous with the ligand base. This method is called incremental construction.

> Using triangles for the ligands’ head and tail sites and matching the proteins’ pocket with the donor - acceptor interaction is what the program does. After the possible solutions are found, the RMSD (root mean square deviation, basically a function of atomic distances) is calculated.

> For scoring or estimating the affinity, many different methods are being used. Force fields approach (has too many paramethers to be calculated, dG intermolecular bonds), Quantum mechanics, statistical approach (you must know some real interactions before), HYDE etc. It is a hot topic in bioinformatics.

[ijtsrd]

The Effect on DNMT1 through Compounds for the Treatment of Cancer An In Silico Approach

by Mishka Tyagi | Noopur Khare | Abhimanyu Kumar Jha "The Effect on DNMT1 through Compounds for the Treatment of Cancer: An In-Silico Approach"

Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-5 | Issue-5 , August 2021,

URL: https://www.ijtsrd.com/papers/ijtsrd43765.pdf

Paper URL: https://www.ijtsrd.com/pharmacy/biotechnology-/43765/the-effect-on-dnmt1-through-compounds-for-the-treatment-of-cancer-an-insilico-approach/mishka-tyagi

callforpaperlifesciences, lifesciencesjournal, researchpapers

Background Cancer is a disease that involves the abnormal gowth of the cell. After growing uncontrollably in continuation, it influences and grows in other parts of the body as well 1,2 . Benign types of Tumors doesn’t invade other body parts whereas Malignant Tumor support spreading and invading other parts of the body 3 . The main objective of this work is to use Molecular Docking method to develop a drug for the treatment of Cancer. Methods Docking was used to dock all the selected ligands with target protein i.e., DNMT1. The selected ligands were Thiophene, Sulfonamides, Chalcone, and Nitroimidazole. PyRx Software was used for the purpose of virtual screening to check various properties of these selected ligands like the Binding Affinity, RMSD Lower Bound , RMSD Upper Bound etc. PyRx and SwissADME both softwares were used for finding out the Drug Likeliness of every compound and to find out the best Compound to be docked with the target protein. Chalcone was found to be the best compound for Cancer treatment having least binding affinity.Results Molecular Docking of Chalcone with DNMT1 protein was performed with the help of AutoDock Vina Software. Output showed 9 positions of different binding affinities and RMSD values both Lower Bound and Upper Bound . Furthermore, the visualization of results was done with the help of PyMOL Software.Conclusion According to this study, Chalcone was the only compound from selected ligands that may be used to treat Cancer. Chalcone may act as a promising drug for cancer treatment in future perspectives. 

[veronika-gold]

Collaborative Book Soul Warrior is getting ready. Hopefully next month is gonna be available on Amazon as e-book. Why I write about it? I wrote I chapter there (3000)words about woman. Woman who is "ME". Believe me or not, but I already got review that my own personal story is boring 🌈 (during one of the pre-read moment). Nothing more courageous than friend opinion before book goes out. 🦄 Well..... I assume I would need to listen my intuition more, then my friend opinion. As always - Intuition takes you into places where friends can't 🎶🎶🎶 Remember that next time someone share their opinion. 😉 @enjoy.yourself.evolution #intuition #collaborativebook #collaboration #soulwarrior #starseed #opinion (at Kitchener, Ontario) https://www.instagram.com/p/CUxJK2-rmsd/?utm_medium=tumblr

[premierteru]

バッファロー microSD 128GB 100MB/s UHS-1 U1 【 Nintendo Switch / ドライブレコーダー 対応 】V10 A1 IPX7 Full HD データ復旧サービス対応 RMSD #Amazon #タイムセール #Amazonタイムセール祭り

バッファロー microSD 128GB 100MB/s UHS-1 U1 【 Nintendo Switch / ドライブレコーダー 対応 】V10 A1 IPX7 Full HD データ復旧サービス対応 RMSD #Amazon #タイムセール #Amazonタイムセール祭り

商品リンク： https://amzn.to/3i8B8Fn

[biodiscovery-group]

Glimpse of ongoing GROMACS, VMD & NAMD | 8 Day Technical Hands-on Certificate Training in MD Simulations A new kind of program on both Windows OS & Linux for a unique learning experience 🎥🎥 Video recording of each session will be provided so to give user a unique learning experience - SELF-PACED - If you miss any session then NO PROBLEM you can still perform the tasks from the video and catch up in the next session. Registration for next one 👉👉 Check out LINK IN BIO . . . . . #envisionwithbdg #itsdifferentbybiodiscovery #bdglifesciences #bioinformaticscompany #10yearsofexcellence #biotechnology #biotech #bioindia #biotechasia #bioinformatics #bioinfo #bioinfoindia #biotechindia #onlinebioinformatics #bioinformaticsworkshop #onlinebioinformaticscourse #bioinformaticsonlinetraining #proteomics #MDSimulations #GROMACS #linux #VMD #NAMD #rmsd #rmsf #radiusofgyration #proteinligandsimulations #Biophysics https://www.instagram.com/p/CTKlKbED68w/?utm_medium=tumblr

[bloghealthcom]

Sự phát triển của 2019-nCoV đang bùng phát ở Vũ Hán và mô hình hóa phân tử protein gai cho thấy nguy cơ lây lan trong cộng đồng người Update 06/2021

Bài viết Sự phát triển của 2019-nCoV đang bùng phát ở Vũ Hán và mô hình hóa phân tử protein gai cho thấy nguy cơ lây lan trong cộng đồng người Update 06/2021 được chia sẻ bởi website Blog-Health #bloghealth #suckhoe #lamdep #sinhly

Bài viết bởi Tiến sĩ Thân Thị Trang Uyên - Chuyên viên Y tế - Tế bào gốc và Tế bào miễn dịch - Phòng dự án sản xuất - Viện Nghiên Cứu Tế Bào Gốc và Công Nghệ Gen Vinmec.

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Tình trạng khẩn cấp về sức khỏe cộng đồng hiện nay một phần giống như sự xuất hiện của dịch SARS ở miền nam Trung Quốc vào năm 2002. Cả hai xảy ra vào mùa đông với các trường hợp ban đầu liên quan đến phơi nhiễm với động vật sống được bán ở chợ động vật và cả hai đều gây ra do các coronavirus chưa biết trước đó.

Ủy ban Y tế thành phố Vũ Hán báo cáo các trường hợp viêm phổi cấp đầu tiên tập trung tại thành phố Vũ Hán, tỉnh Hồ Bắc của Trung Quốc vào ngày 30/12/2019. Các trường hợp viêm phổi được tìm thấy có liên quan đến một chợ hải sản và động vật ở Vũ Hán.

Trung tâm kiểm soát và phòng ngừa dịch bệnh (CDC) và các cơ quan y tế Trung Quốc sau đó đã xác định và thông báo rằng một loại coronavirus mới gọi là Wuhan CoV (2019-nCoV) đã làm bùng phát viêm phổi ở thành phố này. Tình trạng khẩn cấp về sức khỏe cộng đồng hiện nay một phần giống như sự xuất hiện của dịch SARS ở miền nam Trung Quốc vào năm 2002. Cả hai xảy ra vào mùa đông với các trường hợp đầu tiên đều liên quan đến phơi nhiễm với động vật sống được bán ở chợ động vật và cả hai đều gây ra do các coronavirus chưa biết trước đó.

Hình ảnh virus corona chủng mới 2019-nCoV

Trình tự bộ gen của 2019-nCoV được công bố đầu tiên vào ngày 10/1/2020 và sau đó là nhiều công bố bổ sung về trình tự bộ gen của 2019-nCoV. Để hiểu nguồn gốc 2019-nCoV và mối quan hệ di truyền của nó với các loại coronavirus khác, nghiên cứu của nhóm Xintian Xu và cộng sự (công bố ngày 21/1/2020) đã thực hiện phân tích phát sinh chủng loại dựa trên hệ gen coronavirus từ nhiều nguồn khác nhau. Kết quả cho thấy, 2019-nCoV được nhóm vào chi Betacoronavirus trong cây phát sinh chủng loại. Khả năng vật chủ tự nhiên của chúng là dơi và virus SARS/ coronavirus giống SARS (SARS-like coronavirus) có cùng một tổ tiên giống với coronavirus dơi HKU9-1.

Trình tự bộ gen của 2019-nCoV

Để nghiên cứu 2019-nCoV và sự tương tác của chúng với vật chủ, nhóm nghiên cứu đã xem xét vùng liên kết thụ thể (receptor binding domain – RBD) protein gai (S-protein) của 2019-nCoV thấy có một số bản vá trình tự có tính tương đồng cao với SARS-CoV_Tor2 và HP03-GZ01. Các vị trí 438, 472, 479, 487 và 491 của S-protein SARS-CoV được tìm thấy nằm ở vị trí tiếp xúc thụ thể và được coi là rất quan trọng cho việc SARS-CoV truyền chéo giữa các loài và truyền từ người sang người. Tuy nhiên, chỉ có vị trí Tyr491 còn được bảo tồn trong S-protein của 2019-nCoV, còn lại bốn trong số năm vị trí trọng khác không còn được thấy trong 2019-nCoV.

Mô hình cấu trúc vỏ capsid và sợi RNA hệ gen của virus 2019-nCoV

Để đánh giá nguy cơ truyền 2019-nCoV từ người sang người, nhóm nghiên cứu đã lập mô hình cấu trúc protein S của virus và đánh giá khả năng tương tác của nó với các phân tử ACE2 của tế bào người. Mô hình tính toán của protein S của 2019-nCoV Vũ Hán cho thấy độ lệch căn quân phương (RMSD) của Cα là 1,45 Å trên miền RBD so với cấu trúc protein S của SARS-CoV. Năng lượng tự do liên kết giữa protein S của 2019-nCoV và ACE2 người là -50,6 kcal/mol, trong khi đó giữa S-protein của SARS-CoV và ACE2 người là -78,6 kcal/mol. Do mất các tương tác liên kết hydro do thay thế Arg426 bằng Asn426 trong protein S của 2019-nCoV Vũ Hán, năng lượng tự do liên kết cho protein S 2019-nCoV của Vũ Hán tăng 28 kcal/mol khi so sánh với protein S của SARS-CoV. Kết quả này chỉ ra rằng miền RBD của protein S trên 2019-nCoV Vũ Hán hỗ trợ tương tác mạnh mẽ với các phân tử ACE2 người. Do đó, 2019-nCoV Vũ Hán có nguy cơ lây lan đáng kể trong cộng đồng thông qua sự liên kết S-protein 2019-nCoV với ACE2 trên bề mặt tế bào người.

Tài liệu tham khảo:

Xintian Xu, Ping Chen, Jingfang Wang, Jiannan Feng, Hui Zhou, Xuan Li, Wu Zhong & Pei Hao. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China, Life Sciences, Jan 2020.

Để được tư vấn trực tiếp, Quý Khách vui lòng bấm số HOTLINE hoặc đăng ký trực tuyến TẠI ĐÂY. Ngoài ra, Quý khách có thể Đăng ký tư vấn từ xa TẠI ĐÂY

source https://blog-health.com/su-phat-trien-cua-2019-ncov-dang-bung-phat-o-vu-han-va-mo-hinh-hoa-phan-tu-protein-gai-cho-thay-nguy-co-lay-lan-trong-cong-dong-nguoi/

[psyhighdesigns]

Little alien heads are back in stock for Halloween! I'll measure them up tomorrow but it's about 18" long including the collar. UV reactive material with contrasting yellow eyes with embroidered detail. £70 posted rmsd Price includes fan and lamp. https://www.facebook.com/PsyHighInflatables/ https://ebay.co.uk/usr/psyhighdesigns #psyhighdesigns #psyhighinflatables #psyhighdecor #festival #event #music #dance #handmade #ooak #fluorescent #nightclub #neon #night #club #nightlife #RGB #UV #uvreactive #inflatable #inflatables #decor #decoration #cyber #rave #party #partydecorations #partydecor (at Halifax, West Yorkshire) https://www.instagram.com/p/CE4mLd4BbsU/?igshid=1pb2i41sqzpm3