The VSGB 2.0 model: A next generation energy model for high resolution protein structure modeling
TLDR
Given the precision and robustness of the calculations, it is believed that the VSGB 2.0 model is suitable to tackle “real” problems, such as biological function modeling and structure‐based drug discovery.Abstract:
A novel energy model (VSGB 2.0) for high resolution protein structure modeling is described, which features an optimized implicit solvent model as well as physics-based corrections for hydrogen bonding, π-π interactions, self-contact interactions and hydrophobic interactions. Parameters of the VSGB 2.0 model were fit to a crystallographic database of 2239 single side chain and 100 11–13 residue loop predictions. Combined with an advanced method of sampling and a robust algorithm for protonation state assignment, the VSGB 2.0 model was validated by predicting 115 super long loops up to 20 residues. Despite the dramatically increasing difficulty in reconstructing longer loops, a high accuracy was achieved: all of the lowest energy conformations have global backbone RMSDs better than 2.0 A from the native conformations. Average global backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and 1.59 A for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively. When these results are corrected for possible statistical bias as explained in the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06, 1.67, and 1.59 A. Given the precision and robustness of the calculations, we believe that the VSGB 2.0 model is suitable to tackle “real” problems, such as biological function modeling and structure-based drug discovery.read more
Citations
More filters
Journal ArticleDOI
Enhancing Hit Discovery in Virtual Screening through Absolute Protein-Ligand Binding Free-Energy Calculations.
Wei Chen,Steven V. Jerome,Mayako Michino,Eelke B. Lenselink,David J. Huggins,Alexandre Beautrait,Jeremie Vendome,Robert Abel,Richard A. Friesner,Lingle Wang +9 more
TL;DR: In this paper , an accurate and reliable ABFEP method for protein-ligand binding free-energy perturbation (ABFEP) was proposed to improve the hit rates in virtual screening.
Journal ArticleDOI
Molecular dynamics and structure-based virtual screening and identification of natural compounds as Wnt signaling modulators: possible therapeutics for Alzheimer’s disease
Suman Manandhar,Runali Sankhe,Keerthi Priya,Gangadhar Hari,Harish Kumar B,Chetan Hasmukh Mehta,Usha Y. Nayak,K.S.R. Pai +7 more
TL;DR: In this paper , the computational structure-based virtual screening followed by the identification of potential phytomolecules targeting different markers of Wnt signaling like WIF1, DKK1, LRP6, GSK-3β, and acetylcholine esterase was performed.
Journal ArticleDOI
COVID-19 Activity of Some 9-Anilinoacridines substituted with Pyrazole against SARS CoV2 Main Protease: An In-silico Approach
K V Rajagopal,Rajesh Kannan,Baliwada Aparna,Potlapati Varakumar,Arumugasamy Pandiselvi,B. Gowramma +5 more
TL;DR: In this article , pyrazole bearing 9-anilinoacridines (1a-z) were designed by in-silico studies for SARS-CoV-2 Mpro inhibitory activity.
Journal ArticleDOI
In silico and in vitro evaluation of imatinib as an inhibitor for SARS-CoV-2
Nirmitee Mulgaonkar,Haoqi Wang,Samavath Mallawarachchi,Daniel Růžek,Byron E. E. Martina,Sandun Fernando +5 more
TL;DR: This study investigates the interaction of imatinib, a compound under clinical trials for the treatment of COVID-19, with SARS-CoV-2 RBD, and provides significant molecular insights on potential repurposable small-molecule drugs and chemical scaffolds for the development of novel drugs targeting the Sars-Cov-2 spike RBD.
Journal ArticleDOI
A novel KPC-113 variant conferring carbapenem and ceftazidime-avibactam resistance in a multidrug-resistant Pseudomonas aeruginosa isolate.
TL;DR: In this article , a novel KPC-113 variant from a clinical Pseudomonas aeruginosa isolate R20-14 was characterized using Schrödinger diagrams.
References
More filters
Journal ArticleDOI
Comparative Protein Modelling by Satisfaction of Spatial Restraints
Andrej Sali,Tom L. Blundell +1 more
TL;DR: A comparative protein modelling method designed to find the most probable structure for a sequence given its alignment with related structures, which is automated and illustrated by the modelling of trypsin from two other serine proteinases.
Journal ArticleDOI
SWISS-MODEL: an automated protein homology-modeling server
TL;DR: The SWISS-MODEL server is under constant development to improve the successful implementation of expert knowledge into an easy-to-use server.
Journal ArticleDOI
Semianalytical treatment of solvation for molecular mechanics and dynamics
TL;DR: In this paper, it was shown that the active carbon incorporation catalyst is carbided iron and this conclusion was well supported by bulk carbon to iron stoichiometries of 0.1-0.25 estimated from the TPHT peak areas which were adequate to represent 40-60'36 conversion to bulk carbides such as Fe,C or FeSC2.
Journal ArticleDOI
Improved protein-ligand docking using GOLD.
Marcel L. Verdonk,Jason C. Cole,Michael J. Hartshorn,Christopher W. Murray,Richard D. Taylor +4 more
TL;DR: In terms of producing binding energy estimates, the Goldscore function appears to perform better than the Chemscore function and the two consensus protocols, particularly for faster search settings.
Journal ArticleDOI
Funnels, pathways, and the energy landscape of protein folding: A synthesis
TL;DR: The work unifies several previously proposed ideas concerning the mechanism protein folding and delimits the regions of validity of these ideas under different thermodynamic conditions.