Molecular dynamics simulations and linear response theories jointly describe biphasic responses of myoglobin relaxation and reveal evolutionarily conserved frequent communicators

Bang-Chieh Huang; Lee-Wei Yang

doi:10.2142/biophysico.16.0_473

Molecular dynamics simulations and linear response theories jointly describe biphasic responses of myoglobin relaxation and reveal evolutionarily conserved frequent communicators

Biophys Physicobiol. 2019 Nov 29:16:473-484. doi: 10.2142/biophysico.16.0_473. eCollection 2019.

Authors

Bang-Chieh Huang¹, Lee-Wei Yang^{1

2

3

4}

Affiliations

¹ Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 30013, Taiwan.
² Bioinformatics Program, Taiwan International Graduate Program, Institute of Information Sciences, Academia Sinica, Taipei 11529, Taiwan.
³ Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
⁴ Physics Division, National Center for Theoretical Sciences, Hsinchu 30013, Taiwan.

Abstract

In this study, we provide a time-dependent mechanical model, taking advantage of molecular dynamics simulations, quasiharmonic analysis of molecular dynamics trajectories, and time-dependent linear response theories to describe vibrational energy redistribution within the protein matrix. The theoretical description explained the observed biphasic responses of specific residues in myoglobin to CO-photolysis and photoexcitation on heme. The fast responses were found to be triggered by impulsive forces and propagated mainly by principal modes <40 cm^-1. The predicted fast responses for individual atoms were then used to study signal propagation within the protein matrix and signals were found to propagate ~8 times faster across helices (4076 m/s) than within the helices, suggesting the importance of tertiary packing in the sensitivity of proteins to external perturbations. We further developed a method to integrate multiple intramolecular signal pathways and discover frequent "communicators". These communicators were found to be evolutionarily conserved including those distant from the heme.

Keywords: MD simulation; linear response theory; myoglobin; principal component analysis; signal propagation; time-resolved UVRR; vibrational energy transfer.