BEDAM binding free energy predictions for the SAMPL4 octa-acid host challenge.
The binding energy distribution analysis method (BEDAM) protocol has been employed as part of the SAMPL4 blind challenge to predict the binding free energies of a set of octa-acid host-guest complexes. The resulting predictions were consistently judged as some of the most accurate predictions in this category of the SAMPL4 challenge in terms of quantitative accuracy and statistical correlation relative to the experimental values, which were not known at the time the predictions were made. The work has been conducted as part of a hands-on graduate class laboratory session. Collectively the students, aided by automated setup and analysis tools, performed the bulk of the calculations and the numerical and structural analysis. The success of the experiment confirms the reliability of the BEDAM methodology and it shows that physics-based atomistic binding free energy estimation models, when properly streamlined and automated, can be successfully employed by non-specialists.
Department of Chemistry, CUNY Brooklyn College, 2900 Bedford Avenue, Brooklyn, NY, 11210, USA, egallicchio@brooklyn.cuny.edu.
Emilio
E
Gallicchio
Haoyuan
H
Chen
He
H
Chen
Michael
M
Fitzgerald
Yang
Y
Gao
Peng
P
He
Malathi
M
Kalyanikar
Chuan
C
Kao
Beidi
B
Lu
Yijie
Y
Niu
Manasi
M
Pethe
Jie
J
Zhu
Ronald M
RM
Levy
D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods; D006678:HIV / Q000201:enzymology; D015658:HIV Infections / Q000188:drug therapy; D019427:HIV Integrase / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D012984:Software; D013816:Thermodynamics
D019428:HIV Integrase Inhibitors; D019427:HIV Integrase