Paper Info
Title
A Comparative Linear Interaction Energy and MM/PBSA Study on SIRT1-Ligand Binding Free Energy Calculation.
Abstract
Binding free energy (Delta G(bind)) computation can play an important role in prioritizing compounds to be evaluated experimentally on their affinity for target proteins, yet fast and accurate Delta G(bind) calculation remains an elusive task. In this study, we compare the performance of two popular end-point methods, i.e., linear interaction energy (LIE) and molecular mechanics/Poisson Boltzmann surface area (MM/PBSA), with respect to their ability to correlate calculated binding affinities of 27 thieno[3,2-d]pyrimidine-6-carboxamide-derived sirtuin 1 (SIRT1) inhibitors with experimental data. Compared with the standard single trajectory setup of MM/PBSA, our study elucidates that LIE allows to obtain direct ("absolute") values for SIRT1 binding free energies with lower compute requirements, while the accuracy in calculating relative values for Delta G(bind) is comparable (Pearson's r = 0.72 and 0.64 for LIE and MM/PBSA, respectively). We also investigate the potential of combining multiple docking poses in iterative LIE models and find that Boltzmann-like weighting of outcomes of simulations starting from different poses can retrieve appropriate binding orientations. In addition, we find that in this particular case study the LIE and MM/PBSA models can be optimized by neglecting the contributions from electrostatic and polar interactions to the Delta G(bind) calculations.
Year
DOI
Venue
2019
10.1021/acsicim.9b00609
JOURNAL OF CHEMICAL INFORMATION AND MODELING
DocType
Volume
Issue
Journal
59
9
ISSN
Citations 
PageRank 
1549-9596
0
0.34
References 
Authors
0
5
Name
Order
Citations
PageRank
Eko Aditya Rifai100.34
Marc van Dijk211.03
Nico P. E. Vermeulen3204.32
Arry Yanuar401.35
Daan P Geerke57011.47