The structure and dynamics of calmodulin (CaM), with and without Ca<sup>2+</sup> or a 26-residue synthetic peptide M13 comprising the binding domain of skeletal muscle myosin light chain kinase, were studied by inserting an artificial SCN probe group at different sites along both CaM and M13 chains. The IR CN stretching frequency of the probe group displays solvatochromic shifts due to different polarity and hydrogen bonding environments. Comparisons between CN stretching frequencies of each mutant in the different binding states of the CaM/M13 complex showed varying changes in degree of solvent exposure upon binding. In order to gain a more quantitative understanding of IR frequencies and lineshapes at each mutated site, molecular dynamics (MD) simulations were performed using a modified AMBER99SB forcefield in GROMACS, and solvent-accessible surface areas of SCN probe at each mutated site were calculated. Two methods were attempted and compared for IR lineshape simulation: A QM/MM method adapted from Layfield and Hammes-Schiffer and a solvatochromic effective fragment potential (SolEFP) method adapted from Blasiak and Cho. Progress towards understanding the CN signals using these simulation strategies will be discussed.

Cyanylated cysteine as an infrared reporter of protein-peptide interactions: Experimental measurements, molecular dynamics simulations and semi-quantitative calculations of IR lineshape

254th National Meeting (2017)

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