title: Entropy in bimolecular simulations: A comprehensive review of atomic fluctuations-based methods.
abstract: Entropy of binding constitutes a major, and in many cases a detrimental, component of the binding affinity in biomolecular interactions. While the enthalpic part of the binding free energy is easier to calculate, estimating the entropy of binding is further more complicated. A precise evaluation of entropy requires a comprehensive exploration of the complete phase space of the interacting entities. As this task is extremely hard to accomplish in the context of conventional molecular simulations, calculating entropy has involved many approximations. Most of these golden standard methods focused on developing a reliable estimation of the conformational part of the entropy. Here, we review these methods with a particular emphasis on the different techniques that extract entropy from atomic fluctuations. The theoretical formalisms behind each method is explained highlighting its strengths as well as its limitations, followed by a description of a number of case studies for each method. We hope that this brief, yet comprehensive, review provides a useful tool to understand these methods and realize the practical issues that may arise in such calculations.
authors.affiliation: Department of Physics, American University in Cairo, Cairo, Egypt.
authors.forename: Summer
authors.initials: S
authors.lastname: Kassem
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
authors.forename: Marawan
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Department of Physics, American University in Cairo, Cairo, Egypt.
authors.forename: Salah
authors.initials: S
authors.lastname: El-Sheikh
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB, Canada; Li Ka Shing Applied Virology Institute, University of Alberta, Edmonton, AB, Canada. Electronic address: kbarakat@ualberta.ca.
authors.forename: Khaled H
authors.initials: KH
authors.lastname: Barakat
mesh_terms: D003198:Computer Simulation; D019277:Entropy; D008958:Models, Molecular; D015233:Models, Statistical; D008968:Molecular Conformation; D011336:Probability
keywords: Binding affinity; Configurational entropy; Entropy; Mining minima; Normal mode analysis; Quasi harmonics