Extension of the Variational Free Energy Profile and Multistate Bennett Acceptance Ratio Methods for High-Dimensional Potential of Mean Force Profile Analysis

2021 ◽  
Author(s):  
Timothy J. Giese ◽  
Şölen Ekesan ◽  
Darrin M. York
Keyword(s):  
Free Energy ◽  
Profile Analysis ◽  
Potential Of Mean Force ◽  
High Dimensional ◽  
Energy Profile ◽  
Free Energy Profile ◽  
Acceptance Ratio ◽  
Variational Free Energy ◽  
Bennett Acceptance Ratio ◽  
Force Profile

Free energy profile analysis to identify factors activating the aggregation-induced emission of a cyanostilbene derivative

2021 ◽  
Author(s):  
Norifumi Yamamoto
Keyword(s):  
Free Energy ◽  
Profile Analysis ◽  
Energy Profile ◽  
Contributing Factors ◽  
Free Energy Profile ◽  
Aggregation Induced Emission ◽  
Energy Profiles ◽  
Free Energy Profiles

The contributing factors that cause the aggregation-induced emission (AIE) are determined by identifying characteristic differences in the free energy profiles of the AIE processes of the AIE-active E-form of CN-MBE and the inactive Z-form.

Computational Investigation on the MDM2-Idasanutlin Interaction using the Potential of Mean Force method

2021 ◽  
Vol 15 ◽  
Author(s):  
Pundarikaksha Das ◽  
Venkata Satish Kumar Mattaparthi
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Conformational Dynamics ◽  
Umbrella Sampling ◽  
Potential Of Mean Force ◽  
Negative Regulator ◽  
Energy Profile ◽  
Significant Information ◽  
Free Energy Profile ◽  
Binding Characteristics

Background: The Murine Double Minute 2 (MDM2) protein is a well-studied primary negative regulator of the tumor suppressor p53 molecule. Therefore, nowadays, many research studies have focused on the inhibition of MDM2 with potent inhibitors. Idasanutlin (RG7388) is a well-studied small molecule, the antagonist of MDM2 with potential antineoplastic activity. Nevertheless, the highly significant information about the free energy profile, intermediates, and the association of receptor and ligand components in the MDM2-idasanutlin complex remains unclear. Objective: To study the free energy profile of the MDM2-idasanutlin complex in terms of the Potential of Mean Force (PMF) method. Method: We have used the PMF method coupled with umbrella sampling simulations to generate the free energy profile for the association of N-Terminal Domain (NTD) of MDM2 and idasanutlin and a specific reaction coordinate for identifying transition states, intermediates as well as the relative stabilities of the endpoints. We have also determined the binding characteristics and interacting residues at the interface of the MDM2-idasanutlin complex from the Binding Free Energy (BFE) and Per Residue Energy Decomposition (PRED) analyses. Results: The PMF minima for the MDM2-idasanutlin complex was observed at a center of mass (CoM) distance of separation of 11 Å with dissociation energy of 17.5 kcal mol-1. As a function of the distance of separation of MDM2 from idasanutlin. We also studied the conformational dynamics and stability of the NTD of MDM2. We found a high binding affinity between MDM2 and idasanutlin (∆Grinding = -3.19 kcal mol-1). We found that in MDM2, the residues MET54, VAL67, and LEU58 provide the highest energy input for the interaction between MDM2 and idasanutlin. Conclusion: Our results in this study illustrate the significant structural and binding features of the MDM2-idasanutlin complex that may be useful in developing potent inhibitors of MDM2.

scholarly journals Nonequilibrium study of the intrinsic free-energy profile across a liquid-vapour interface

2016 ◽  
Vol 144 (4) ◽  
pp. 044703 ◽  
Author(s):  
Carlos Braga ◽  
Jordan Muscatello ◽  
Gabriel Lau ◽  
Erich A. Müller ◽  
George Jackson
Keyword(s):  
Free Energy ◽  
Energy Profile ◽  
Free Energy Profile
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