Abstract
The strength of key interfacial contacts that stabilize protein–protein interactions have been studied by computer simulation. Experimentally, changes in the interface are evaluated by generating specific mutations at one or more points of the protein structure. Here, such an evaluation is performed by means of steered molecular dynamics and use of a dimeric model of tryptophan repressor and in-silico mutants as a test case. Analysis of four particular cases shows that, in principle, it is possible to distinguish between wild-type and mutant forms by examination of the total energy and force–extension profiles. In particular, detailed atomic level structural analysis indicates that specific mutations at the interface of the dimeric model (positions 19 and 39) alter interactions that appear in the wild-type form of tryptophan repressor, reducing the energy and force required to separate both subunits.
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Acknowledgments
The authors gratefully thank Fondo Nacional de Desarrollo Científico y Tecnologíco, Fondecyt Grants no. 3110149 (GM), 11110534 (MB). GG acknowledges partial support of Fondecyt-Chile 1120603. This work have also been supported by the High-Performance Computing infrastructure of the Center for Mathematical Modeling, University of Chile, via the Project BASAL-CMM. The authors warmly thank Professors Boris Weiss-López and Bruce Kennedy Cassels for their useful insight and for critical reading of the manuscript.
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Miño, G., Baez, M. & Gutierrez, G. Effect of mutation at the interface of Trp-repressor dimeric protein: a steered molecular dynamics simulation. Eur Biophys J 42, 683–690 (2013). https://doi.org/10.1007/s00249-013-0918-9
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DOI: https://doi.org/10.1007/s00249-013-0918-9