SMoG:  de Novo Design Method Based on Simple, Fast, and Accurate Free Energy Estimates. 1. Methodology and Supporting Evidence

1996 ◽  
Vol 118 (47) ◽  
pp. 11733-11744 ◽  
Author(s):  
Robert S. DeWitte ◽  
Eugene I. Shakhnovich
Keyword(s):  
Free Energy ◽  
De Novo ◽  
Design Method ◽  
De Novo Design ◽  
Energy Estimates ◽  
Supporting Evidence

Structure-based de novo design and identification of D816V mutant-selective c-KIT inhibitors

2014 ◽  
Vol 12 (26) ◽  
pp. 4644-4655 ◽  
Author(s):  
Hwangseo Park ◽  
Soyoung Lee ◽  
Suhyun Lee ◽  
Sungwoo Hong
Keyword(s):  
Free Energy ◽  
Inhibitory Activity ◽  
High Selectivity ◽  
De Novo ◽  
Scoring Function ◽  
Solvation Free Energy ◽  
De Novo Design ◽  
Gain Of Function

New 7-azaindole-based c-KIT inhibitors with nanomolar inhibitory activity and high selectivity for the gain-of-function D816V mutant were identified through the structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy.

Chemical-Space-Based de Novo Design Method To Generate Drug-Like Molecules

2016 ◽  
Vol 56 (10) ◽  
pp. 1885-1893 ◽  
Author(s):  
Shunichi Takeda ◽  
Hiromasa Kaneko ◽  
Kimito Funatsu
Keyword(s):  
De Novo ◽  
Chemical Space ◽  
Design Method ◽  
De Novo Design

A novel human scFv fragment against TNF-α from de novo design method

2007 ◽  
Vol 44 (15) ◽  
pp. 3789-3796 ◽  
Author(s):  
Hong Chang ◽  
Weisong Qin ◽  
Yan Li ◽  
Jiyan Zhang ◽  
Zhou Lin ◽  
...  
Keyword(s):  
De Novo ◽  
Design Method ◽  
De Novo Design ◽  
Scfv Fragment ◽  
Tnf Α ◽  
Human Scfv

SAMPL7 TrimerTrip Host-Guest Binding Poses and Binding Affinities from Spherical-Coordinates-Biased Simulations

2020 ◽  
Author(s):  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Computational Modelling ◽  
Free Energy Calculations ◽  
Energy Estimates ◽  
Binding Affinities ◽  
Spherical Coordinates ◽  
Collective Variables ◽  
Guest Binding ◽  
Starting Point ◽  
Sampl Challenge

Host-guest binding remains a major challenge in modern computational modelling. The newest 7<sup>th</sup> statistical assessment of the modeling of proteins and ligands (SAMPL) challenge contains a new series of host-guest systems. The TrimerTrip host binds to 16 structurally diverse guests. Previously, we have successfully employed the spherical coordinates as the collective variables coupled with the enhanced sampling technique metadynamics to enhance the sampling of the binding/unbinding event, search for possible binding poses and predict the binding affinities in all three host-guest binding cases of the 6<sup>th</sup> SAMPL challenge. In this work, we employed the same protocol to investigate the TrimerTrip host in the SAMPL7 challenge. As no binding pose is provided by the SAMPL7 host, our simulations initiate from randomly selected configurations and are proceeded long enough to obtain converged free energy estimates and search for possible binding poses. The predicted binding affinities are in good agreement with the experimental reference, and the obtained binding poses serve as a nice starting point for end-point or alchemical free energy calculations.

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