Abstrait

Charged Amino Acids: Controlling the Actions

Lakshya Sharma

The actions of integral and peripheral membrane proteins, as well as cell disrupting peptides, are known to be influenced by charged amino acids. Although atomistic molecular dynamics studies have shed light on the mechanics of charged protein group membrane binding and translocation, the impact of the complete range of membrane Physio-chemical characteristics and topologies has yet to be investigated. We investigated the movement of an Arginine (Arg) side chain analogue across saturated phosphatidylcholine (PC) bilayers with hydrocarbon tail lengths ranging from 10 to 18 carbons in this paper. With increased penetration into the hydrocarbon core, the free energy profiles all show steep climbs, with predictable shifts between bilayers of varying thickness, resulting in a barrier reduction from 26 kcal/mol for 18 carbons to 6 kcal/mol for 10 carbons. We see narrow transmembrane pores and associated plateaus in the free energy profiles for lipids with 10 and 12 carbons. Allowing for protein mobility and side-chain snorkelling, we propose that the energy cost of burying Arg inside a thin bilayer will be negligible, resulting in a substantial reduction in pKa changes for Arg, which is consistent with recent findings.