title: Molecular dynamics study of naturally existing cavity couplings in proteins.
abstract: Couplings between protein sub-structures are a common property of protein dynamics. Some of these couplings are especially interesting since they relate to function and its regulation. In this article we have studied the case of cavity couplings because cavities can host functional sites, allosteric sites, and are the locus of interactions with the cell milieu. We have divided this problem into two parts. In the first part, we have explored the presence of cavity couplings in the natural dynamics of 75 proteins, using 20 ns molecular dynamics simulations. For each of these proteins, we have obtained two trajectories around their native state. After applying a stringent filtering procedure, we found significant cavity correlations in 60% of the proteins. We analyze and discuss the structure origins of these correlations, including neighbourhood, cavity distance, etc. In the second part of our study, we have used longer simulations (≥100 ns) from the MoDEL project, to obtain a broader view of cavity couplings, particularly about their dependence on time. Using moving window computations we explored the fluctuations of cavity couplings along time, finding that these couplings could fluctuate substantially during the trajectory, reaching in several cases correlations above 0.25/0.5. In summary, we describe the structural origin and the variations with time of cavity couplings. We complete our work with a brief discussion of the biological implications of these results.
authors: Translational Bioinformatics in Neurosciences, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
authors: Montserrat
authors: M
authors: Barbany
authors: Theoretische und computergestützte Biophysik, Max-Planck-Institut für biophysikalische Chemie, Göttingen, Germany.
authors: Tim
authors: T
authors: Meyer
authors: Joint IRB (Institute for Research in Biomedicine)-BSC (Barcelona Supercomputing Center) Program on Computational Biology, Barcelona, Spain.
authors: Adam
authors: A
authors: Hospital
authors: Joint IRB (Institute for Research in Biomedicine)-BSC (Barcelona Supercomputing Center) Program on Computational Biology, Barcelona, Spain.
authors: Ignacio
authors: I
authors: Faustino
authors: Department of Chemistry, Università degli Studi di Roma "La Sapienza", Roma, Italy.
authors: Marco
authors: M
authors: D'Abramo
authors: Centre for Research in Agricultural Genomics (CRAG), Barcelona, Spain.
authors: Jordi
authors: J
authors: Morata
authors: Joint IRB (Institute for Research in Biomedicine)-BSC (Barcelona Supercomputing Center) Program on Computational Biology, Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.
authors: Modesto
authors: M
authors: Orozco
authors: Translational Bioinformatics in Neurosciences, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors: Xavier
authors: X
authors: de la Cruz
mesh_terms: D000495:Allosteric Site; D000818:Animals; D019143:Evolution, Molecular; D005634:Fructose-Bisphosphate Aldolase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011506:Proteins; D005634:Fructose-Bisphosphate Aldolase