title: Temperature-Dependent Conformational Properties of Human Neuronal Calcium Sensor-1 Protein Revealed by All-Atom Simulations.
abstract: Neuronal calcium sensor-1 (NCS-1) protein has orthologues from Saccharomyces cerevisiae to human with highly conserved amino acid sequences. NCS-1 is an important factor controlling the animal's response to temperature change. This leads us to investigate the temperature effects on the conformational dynamics of human NCS-1 at 310 and 316 K by all-atom molecular dynamics (MD) simulations and dynamic community network analysis. Four independent 500 ns MD simulations show that secondary structure content at 316 K is similar to that at 310 K, whereas the global protein structure is expanded. Loop 3 (L3) adopts an extended state occuping the hydrophobic crevice, and the number of suboptimal communication paths between residue D176 and V190 is reduced at 316 K. The dynamic community network analysis suggests that the interdomain correlation is weakened, and the intradomain coupling is strengthened at 316 K. The elevated temperature reduces the number of the salt bridges, especially in C-domain. This study suggests that the elevated temperature affects the conformational dynamics of human NCS-1 protein. Comparison of the structural dynamics of R102Q mutant and Δ176-190 truncated NCS-1 suggests that the structural and dynamical response of NCS-1 protein to elevated temperature may be one of its intrinsic functional properties.
authors.affiliation: College of Physical Education and Training, Shanghai University of Sport , 399 Chang Hai Road, Shanghai 200438, China.
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute , Frederick, Maryland 21702, United States.
authors.forename: Buyong
authors.initials: B
authors.lastname: Ma
authors.affiliation: Department of Physics, Fudan University , 220 Handan Road, Shanghai 200433, China.
authors.forename: Ruxi
authors.initials: R
authors.lastname: Qi
authors.affiliation: Basic Science Program, Leidos Biomedical Research, Inc. Cancer and Inflammation Program, National Cancer Institute , Frederick, Maryland 21702, United States.|Sackler Inst. of Molecular Medicine Department of Human Genetics and Molecular Medicine Sackler School of Medicine, Tel Aviv University , Tel Aviv 69978, Israel.
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.affiliation: College of Physical Education and Training, Shanghai University of Sport , 399 Chang Hai Road, Shanghai 200438, China.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D004220:Disulfides / Q000737:chemistry; D006801:Humans; D056004:Molecular Dynamics Simulation; D051580:Neuronal Calcium-Sensor Proteins / Q000737:chemistry* / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry* / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D004220:Disulfides; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; C101464:frequenin calcium sensor proteins