Molecular modeling and dynamic simulation of chicken Mx protein with the S631N polymorphism

Abstract

Myxovirus resistance (Mx) proteins are antiviral GTPases induced by type I interferons (IFNs). In chickens, a single Mx protein variant, S631N, has been suggested to possess antiviral activity. However, the impact of this variant on chicken Mx (chMx) protein structure and conformation has not been investigated. Hence, in this study, we applied computational methods such as molecular modeling, molecular dynamic simulation, inter domain motion and residue networks to examine the structure and dynamic behavior of wild-type and mutant chMx. At first, we built 3-dimensional structural models for both wild-type and mutant chMx proteins, which revealed that the structural organization of chMx was similar to that of human Mx proteins. Subsequently, molecular dynamics simulations revealed that angle variation around the hinge1 region led to the different stalk domain conformations between the wild-type and mutant chMx proteins. Domain motion analysis further suggested that the conformational differences in the loop region surrounded by the mutant residue may lead to an inclined stalk domain conformation in the mutant compared to the wild-type protein. In addition, we performed betweenness centrality analysis from residue interaction networks, to identify the crucial residues for intramolecular signal flow in chMx. The results of this study provided information on the differences in structure and dynamics between wild-type and mutant chMx, which may aid in understanding the structural features of the S631N mutant, that may be associated with chMx protein antiviral activity.

Communicated by Ramaswamy H. Sarma

Keywords:

• Mx protein
• polymorphism
• molecular dynamics simulation
• essential dynamics
• interdomain motion
• residue networks

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This research was funded by the Next-Generation Biogreen 21 Program, Rural Development Administration, Republic of Korea, grant numbers PJ013151 and PJ01324201 and the National Research Foundation of Korea, grant number NRF-2018R1C1B6008141.