Essence of Small Molecule-Mediated Control of Hydroxyapatite Growth: Free Energy Calculations of Amino Acid Side Chain Analogues

2018 ◽  
Vol 122 (8) ◽  
pp. 4372-4380 ◽  
Author(s):  
Zhijun Xu ◽  
Qichao Wei ◽  
Weilong Zhao ◽  
Qiang Cui ◽  
Nita Sahai
Keyword(s):  
Free Energy ◽  
Amino Acid ◽  
Small Molecule ◽  
Free Energy Calculations ◽  
Side Chain ◽  
Amino Acid Side Chain ◽  
Energy Calculations

scholarly journals QligFEP: an automated workflow for small molecule free energy calculations in Q

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Willem Jespers ◽  
Mauricio Esguerra ◽  
Johan Åqvist ◽  
Hugo Gutiérrez-de-Terán
Keyword(s):  
Free Energy ◽  
Small Molecule ◽  
Free Energy Calculations ◽  
Energy Calculations

scholarly journals Challenges Encountered Applying Equilibrium and Non-Equilibrium Binding Free Energy Calculations

2020 ◽  
Author(s):  
Hannah Baumann ◽  
Vytautas Gapsys ◽  
Bert L. de Groot ◽  
David Mobley
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Side Chain ◽  
Future Research ◽  
Energy Calculations ◽  
Binding Free Energy Calculations ◽  
Sampling Problems ◽  
Alchemical Free Energy ◽  
Non Equilibrium

<div>Binding free energy calculations have become increasingly valuable to drive decision making in drug discovery projects. </div><div>However, among other issues, inadequate sampling can reduce accuracy, limiting the value of the technique.</div><div>In this paper we apply absolute binding free energy calculations to ligands binding to T4 lysozyme L99A and HSP90 using equilibrium and non-equilibrium approaches. We highlight sampling problems encountered in these systems, such as slow side chain rearrangements and slow changes of water placement upon ligand binding. These same types of challenges are likely to show up in other protein-ligand systems as well and we propose some strategies to diagnose and test for such problems in alchemical free energy calculations. We also explore similarities and differences in how the equilibrium and the non-equilibrium approaches handle these problems. Our results show the large amount of work still to be done to make free energy calculations robust and reliable and provide insight for future research in this area. </div>

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