TY - JOUR
T1 - Intrinsically Disordered Landscapes for Human CD4 Receptor Peptide
AU - Joseph, Jerelle A.
AU - Wales, David J.
N1 - Funding Information:
The authors thank B. E. Husic and D. Chakraborty for useful comments and suggestions during the preparation of the manuscript. J.A.J. acknowledges financial support from the Gates Cambridge Trust. D.J.W. gratefully acknowledges support from the EPSRC.
Publisher Copyright:
© Copyright 2018 American Chemical Society.
PY - 2018/12/20
Y1 - 2018/12/20
N2 - Because of their inherent structural plasticity, intrinsically disordered proteins (IDPs) are generally difficult to characterize, both experimentally and via simulations. In this work, an approach for studying IDPs within the potential energy landscape framework is implemented and tested. Specifically, human CD4 receptor peptide, a disordered region implicated in HIV-1 infection, is characterized via basin-hopping parallel tempering and discrete path sampling. We also investigate the effects of three state-of-the-art AMBER force fields (ff99SB-ILDN, ff14ipq, and ff14SB) on the energy landscape. The results for ff99SB-ILDN exhibit the best agreement with experiment. Metastable states identified on the free energy surface help to unify, and are consistent with, several earlier predictions, and may serve as starting points for probing the reaction interface between CD4 and HIV-1 accessory proteins.
AB - Because of their inherent structural plasticity, intrinsically disordered proteins (IDPs) are generally difficult to characterize, both experimentally and via simulations. In this work, an approach for studying IDPs within the potential energy landscape framework is implemented and tested. Specifically, human CD4 receptor peptide, a disordered region implicated in HIV-1 infection, is characterized via basin-hopping parallel tempering and discrete path sampling. We also investigate the effects of three state-of-the-art AMBER force fields (ff99SB-ILDN, ff14ipq, and ff14SB) on the energy landscape. The results for ff99SB-ILDN exhibit the best agreement with experiment. Metastable states identified on the free energy surface help to unify, and are consistent with, several earlier predictions, and may serve as starting points for probing the reaction interface between CD4 and HIV-1 accessory proteins.
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U2 - 10.1021/acs.jpcb.8b08371
DO - 10.1021/acs.jpcb.8b08371
M3 - Article
C2 - 30433786
AN - SCOPUS:85058660601
SN - 1520-6106
VL - 122
SP - 11906
EP - 11921
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 50
ER -