Molecular simulations of venom peptide‐membrane interactions: Progress and challenges

Abstract

Because of their wide range of biological activities venom peptides are a valuable source of lead molecules for the development of pharmaceuticals, pharmacological tools and insecticides. Many venom peptides work by modulating the activity of ion channels and receptors or by irreversibly damaging cell membranes. In many cases, the mechanism of action is intrinsically linked to the ability of the peptide to bind to or partition into membranes. Thus, understanding the biological activity of these venom peptides requires characterizing their membrane binding properties. This review presents an overview of the recent developments and challenges in using biomolecular simulations to study venom peptide‐membrane interactions. The review is focused on (i) gating modifier peptides that target voltage‐gated ion channels, (ii) venom peptides that inhibit mechanosensitive ion channels, and (iii) pore‐forming venom peptides. The methods and approaches used to study venom peptide‐membrane interactions are discussed with a particular focus on the challenges specific to these systems and the type of questions that can (and cannot) be addressed using state‐of‐the‐art simulation techniques. The review concludes with an outlook on future aims and directions in the field.

Snake Venom-Derived Peptides as Prospective Pharmacological Tools: Recent Trends

“…It is mainly classified into type 1 diabetes and type 2 diabetes and 90-95% diabetic patients are type 2 diabetes mellitus is characterized by insulin resistance, which result in decreasing insulin actions on targeted tissues [147]. Recently, diverse venom peptides have emerged as pharmacological implements and remedial for type 1 diabetes and type 2 diabetes [148]. N. atra venom is known to reduce hyperglycemia, decrease urinary protein, enhance renal function and structure, prevent oxidative stress and lipid metabolism products, and restrict inflammatory factor infiltration in Wistar rats [149].…”

The unusual conformation of cross‐strand disulfide bonds is critical to the stability of β‐hairpin peptides

“…Peptides and proteins with structural properties that deviate from the norm can pose challenges for biomolecular simulations [51][52][53]. Molecular dynamics (MD) simulations are extensively used to study peptides and their interactions with proteins or biological membranes [53][54][55][56][57]. The accuracy of properties obtained from MD simulations, amongst other factors, strongly depends on the force field used [51,52,58,59].…”

Revisiting the Interaction of Melittin with Phospholipid Bilayers: The Effects of Concentration and Ionic Strength

“…A two-step model is often used to describe the mechanism of formation of membrane pores by melittin [26,41,42], wherein the peptide, at low concentration, binds to the bilayer surface in a parallel conformation and then shifts to a perpendicular orientation at higher concentration, leading to membrane pore formation. The existence of two membrane-bound orientations has been demonstrated by molecular simulation studies [43][44][45][46][47][48] and the retention of amphiphilic peptides in a surface-absorbed state has been explained by elasticity theory [49].…”