Influence of cis douple-bond parametrization on lipid membrane properties: How seemingly insignificant details in force-field change even qualitative trends

We have employed atomistic molecular dynamics simulations to investigate the effect of double-bond parametrization on lipid membrane properties. As models, we use one-component membranes composed of glycerol-based phosphatidylcholines (PCs) with monounsaturated acyl chains, and we complement these studies by additional PC/cholesterol simulations. We compare differences between double-bond parametrizations by varying the position of the double bond systematically along the lipid hydrocarbon chains. The results give rise for concern: They indicate that the double-bond description may change not only the quantitative but also the qualitative nature of membrane behavior. In particular, we find that the double-bond description which accounts for skew states in the vicinity of a double bond predicts a maximum in membrane disorder, when the double bond resides at the middle of an acyl chain, in agreement with experiments. The more commonly used description which does not accommodate skew states, however, predicts membrane disorder to decrease monotonically as the double bond is shifted from the glycerol backbone to the end of an acyl chain. The results highlight the importance of properly describing double bonds especially in many-component membranes, where the interplay of different molecule types is difficult to predict on intuitive grounds.Peer reviewe