Membrane-active peptides (MAPs) represent a broad variety of molecules, and biological functions of most are
directly associated with their ability to interact with membranes. Taking into account the effect of MAPs on living cells
they can be nominally divided into three major groups – fusion (FPs), antimicrobial/cytolytic (AMPs/CPs) and cellpenetrating
(CPPs) peptides. Although spatial structure of different MAPs varies to a great extent, linear α-helical peptides
represent the most studied class. These peptides possess relatively simple structural organization and share a set of
similar molecular features, which make them very attractive to both experimental and computational studies. Here, we review
different molecular modeling methods in prospective of their applications to study of α-helical MAPs. The most sophisticated
of them, such as molecular dynamics simulations, give atomistic information about molecular interactions
driving peptide binding to the water-lipid interface, cooperative mechanisms of membrane destabilization and thermodynamics
of these processes. Significant progress has been achieved in this field during the last few years, resulting in a possibility
to observe computationally MAPs action in realistic peptide-to-lipid ratios and over the microsecond timescale.
Other relatively simple but powerful approaches allow assessment of important characteristics of MAPs such as α-helical
propensity, amphiphilicity, total hydrophobicity, and spatial distribution of charge and hydrophobic/hydrophilic properties,
etc. Altogether, computational methods provide efficient basis for rational design of MAPs with predefined properties
and a spectrum of biological activities.