Advances in theoretical chemistry have led to the development of various robust computational techniques employed in drug design. Pharmacophore modeling, molecular docking, and molecular dynamics (MD) simulations have been extensively applied, separately or in combination, in the design of potent molecules. The techniques involve the identification of a potential drug target (e.g., protein) and its subsequent characterization. The next step in the process comprises the development of a map describing the interaction patterns between the target molecule and its natural substrate. Once these key features are identified, it is possible to explore the map and screen large databases of molecules to identify potential drug candidates for further refinement.Multiple sclerosis (MS) is an autoimmune disease where the immune system attacks the myelin sheath of nerve cells. The process involves the activation of encephalitogenic T cells via the formation of the trimolecular complex between the human leukocyte antigen (HLA), an immunodominant epitope of myelin proteins, and the T-cell receptor (TCR). Herein, the process for rational design and development of altered peptide ligands (APLs) and non-peptide mimetics against MS is described through the utilization of computational methods.
Keywords: Docking; Molecular dynamics; Multiple sclerosis; Peptide mimetics; Pharmacophore modeling.