Investigating the effect of charged amino acids on DNA conformation in EcoRI–DNA complex: a molecular dynamics simulation study

Abstract

Sequence-specific binding of proteins to DNA is essential for almost all the cellular processes like transcription, translation, replication, etc. One among the various mechanisms that has been identified so far that contributes to the specificity in protein–DNA interaction is the DNA conformational change. Electrostatic neutralization of the phosphate groups by the positively charged amino acid residues in proteins is thought to bring about such conformational changes in DNA. Here, we employ molecular dynamics simulations to examine the effect of charge on amino acids Lys113, Arg145, and Asp91 which are attached to the scissile phosphate on the conformation of DNA in EcoRI–DNA complex. The results indicate that the charge of these amino acids is essential for maintaining the local conformation of DNA in the EcoRI-bound form. Interestingly, we observe that the positively charged amino acids Lys113 and Arg145 have a long-range influence on the DNA conformation, whereas the negatively charged amino acid Asp91 has only a localized effect on the DNA conformation. The charge on the amino acids also alters the collective dynamics of EcoRI. Collectively, the results shed light on the diversity of the effect of charges on DNA conformation as well as on protein dynamics.

Keywords:

• DNA kinks
• essential dynamics
• molecular dynamics
• partial neutralization
• inner product matrix

Acknowledgments

SR acknowledges Mr R. Senthilnathan for technical help in using the R software. We thank the anonymous reviewers whose comments and suggestions helped us improve the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by the Department of Science and Technology (DST) under the grant (DST-SERB Fast Track grant number SB/FT/LS-436/2012) and SASTRA University under the TRR Grant.