Anomeric Free Energy ofd-Mannose in Water:  A Comparison of Free Energy Perturbation, Potential of Mean Force, and MC(JBW)/SD Simulations

1997 ◽  
Vol 101 (8) ◽  
pp. 1409-1412 ◽  
Author(s):  
Hanoch Senderowitz ◽  
W. Clark Still
Keyword(s):  
Free Energy ◽  
Potential Of Mean Force ◽  
Free Energy Perturbation ◽  
Perturbation Potential ◽  
Energy Perturbation

scholarly journals A computational study of barium blockades in the KcsA potassium channel based on multi-ion potential of mean force calculations and free energy perturbation

2013 ◽  
Vol 142 (4) ◽  
pp. 451-463 ◽  
Author(s):  
Christopher N. Rowley ◽  
Benoît Roux
Keyword(s):  
Free Energy ◽  
Computational Study ◽  
Potential Of Mean Force ◽  
Free Energy Perturbation ◽  
K Channel ◽  
Rate Theory ◽  
Crystallographic Structure ◽  
Energy Perturbation ◽  
Lock In Effect ◽  
Lock In

Electrophysiological studies have established that the permeation of Ba2+ ions through the KcsA K+-channel is impeded by the presence of K+ ions in the external solution, while no effect is observed for external Na+ ions. This Ba2+ “lock-in” effect suggests that at least one of the external binding sites of the KcsA channel is thermodynamically selective for K+. We used molecular dynamics simulations to interpret these lock-in experiments in the context of the crystallographic structure of KcsA. Assuming that the Ba2+ is bound in site S2 in the dominant blocked state, we examine the conditions that could impede its translocation and cause the observed “lock-in” effect. Although the binding of a K+ ion to site S1 when site S2 is occupied by Ba2+ is prohibitively high in energy (>10 kcal/mol), binding to site S0 appears to be more plausible (ΔG > 4 kcal/mol). The 2D potential of mean force (PMF) for the simultaneous translocation of Ba2+ from site S2 to site S1 and of a K+ ion on the extracellular side shows a barrier that is consistent with the concept of external lock-in. The barrier opposing the movement of Ba2+ is very high when a cation is in site S0, and considerably smaller when the site is unoccupied. Furthermore, free energy perturbation calculations show that site S0 is selective for K+ by 1.8 kcal/mol when S2 is occupied by Ba2+. However, the same site S0 is nonselective when site S2 is occupied by K+, which shows that the presence of Ba2+ affects the selectivity of the pore. A theoretical framework within classical rate theory is presented to incorporate the concentration dependence of the external ions on the lock-in effect.

scholarly journals Free energy perturbation calculations on binding and catalysis after mutating threonine 220 in subtilisin

1991 ◽  
Vol 266 (18) ◽  
pp. 11801-11809
Author(s):  
N. Mizushima ◽  
D. Spellmeyer ◽  
S. Hirono ◽  
D. Pearlman ◽  
P. Kollman
Keyword(s):  
Free Energy ◽  
Free Energy Perturbation ◽  
Energy Perturbation

scholarly journals Potent Noncovalent Inhibitors of the Main Protease of SARS-CoV-2 from Molecular Sculpting of the Drug Perampanel Guided by Free Energy Perturbation Calculations

2021 ◽  
Vol 7 (3) ◽  
pp. 467-475 ◽  
Author(s):  
Chun-Hui Zhang ◽  
Elizabeth A. Stone ◽  
Maya Deshmukh ◽  
Joseph A. Ippolito ◽  
Mohammad M. Ghahremanpour ◽  
...  
Keyword(s):  
Free Energy ◽  
Free Energy Perturbation ◽  
Main Protease ◽  
Energy Perturbation

Thrombin Inhibition by Novel Benzamidine Derivatives:  A Free-Energy Perturbation Study

2002 ◽  
Vol 45 (23) ◽  
pp. 4995-5004 ◽  
Author(s):  
Cristiano Ruch Werneck Guimarães ◽  
Ricardo Bicca de Alencastro
Keyword(s):  
Free Energy ◽  
Free Energy Perturbation ◽  
Thrombin Inhibition ◽  
Energy Perturbation
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