Discrete analyses of protein dynamics

Abstract

Protein structures are highly dynamic macromolecules. This dynamics is often analysed through experimental and/or computational methods only for an isolated or a limited number of proteins. Here, we explore large-scale protein dynamics simulation to observe dynamics of local protein conformations using different perspectives. We analysed molecular dynamics to investigate protein flexibility locally, using classical approaches such as RMSf, solvent accessibility, but also innovative approaches such as local entropy. First, we focussed on classical secondary structures and analysed specifically how β-strand, β–turns, and bends evolve during molecular simulations. We underlined interesting specific bias between β–turns and bends, which are considered as the same category, while their dynamics show differences. Second, we used a structural alphabet that is able to approximate every part of the protein structures conformations, namely protein blocks (PBs) to analyse (i) how each initial local protein conformations evolve during dynamics and (ii) if some exchange can exist among these PBs. Interestingly, the results are largely complex than simple regular/rigid and coil/flexible exchange.

Abbreviations
N eq	=	number of equivalent
PB	=	Protein Blocks
PDB	=	Protein DataBank
RMSf	=	root mean square fluctuations

Communicated by Ramaswamy H. Sarma

Keywords:

• Local protein conformations
• structural alphabet
• molecular dynamics
• disorder
• flexibility
• secondary structure
• Protein DataBank
• solvent accessibility

Acknowledgments

The authors would like to thanks Nenad Mitić, organizers and participants of Belbi’2016 and Belbi’2018 for fruitful discussions, and Snoopy for the pictures. This work was supported by grants from the Ministry of Research (France), University Paris Diderot, Sorbonne, Paris Cité (France), National Institute for Blood Transfusion (INTS, France), National Institute for Health and Medical Research (INSERM, France) and labex GR-Ex. The labex GR-Ex, reference ANR-11-LABX-0051 is funded by the program ‘Investissements d’avenir’ of the French National Research Agency, reference ANR-11-IDEX-0005-02. T. J. N., N. S. and A. d. B. acknowledge to Indo-French Centre for the Promotion of Advanced Research/CEFIPRA for collaborative grant (number 5302-2). This work is supported by a grant from the French National Research Agency (ANR): NaturaDyRe (ANR-2010-CD2I-014-04) to J. R. and A. d. B. N. S. h. acknowledges support from ANRT. A. M. V. is supported by Allocation de Recherche Réunion granted by the Conseil Régional de la Réunion and the European Social Fund EU (ESF). N. S. is supported by Mathematical Biology program and FIST program sponsored by the Department of Science and Technology and also by the Department of Biotechnology, Government of India in the form of IISc-DBT partnership programme. Support from UGC, India – Centre for Advanced Studies and Ministry of Human Resource Development, India is gratefully acknowledged by N. S. N. S. is a J. C. Bose National Fellow.

Disclosure statement

The authors have no conflict of interest to declare. J. C. G. and A. D. B. are associated with IBL, Paris, France.

Additional information

Funding

The authors were granted access to high performance computing (HPC) resources at the French National Computing Centre CINES under grant no. c2013037147, no. A0010707621 and A0040710426 funded by the GENCI (Grand Equipement National de Calcul Intensif). Calculations were also performed on an SGI cluster granted by Conseil Régional Ile de France and INTS (SESAME Grant).