In silico methods for design of biological therapeutics

Abstract

It has been twenty years since the first rationally designed small molecule drug was introduced into the market. Since then, we have progressed from designing small molecules to designing biotherapeutics. This class of therapeutics includes designed proteins, peptides and nucleic acids that could more effectively combat drug resistance and even act in cases where the disease is caused because of a molecular deficiency. Computational methods are crucial in this design exercise and this review discusses the various elements of designing biotherapeutic proteins and peptides. Many of the techniques discussed here, such as the deterministic and stochastic design methods, are generally used in protein design. We have devoted special attention to the design of antibodies and vaccines. In addition to the methods for designing these molecules, we have included a comprehensive list of all biotherapeutics approved for clinical use. Also included is an overview of methods that predict the binding affinity, cell penetration ability, half-life, solubility, immunogenicity and toxicity of the designed therapeutics. Biotherapeutics are only going to grow in clinical importance and are set to herald a new generation of disease management and cure.

Engineering Stability, Viscosity, and Immunogenicity of Antibodies by Computational Design

“…However, because of recent advances in computational power and algorithms, computational design is becoming an alternative method in antibody engineering. [13][14][15][16][17][18] One of the advantages to computational methods is that their use can be a rational approach when combined with a structure. Antibodies and their structures should be governed by physical laws, and based on physical principles, we should be able to predict behavior of antibodies in solution and in our body.…”

Novel Angiotensin‐Converting Enzyme Inhibitory Peptides Derived from Oncorhynchus mykiss Nebulin: Virtual Screening and In Silico Molecular Docking Study

“…Nowadays, in silico tools were used to identify food‐derived bioactive peptides in emerging nutraceutical field, including smooth‐hound viscera protein (Abdelhedi et al., ), ACE inhibitory peptide from silkworm pupa (Tao et al., ), prolyl endopeptidase inhibitors from meat (Lafarga, O'Connor, & Hayes, ), antioxidative collagen peptides from carp swim bladder (Roy, Nair, Sen, Soni, & Madhusudhan, ), and antihypertensive oligopeptides from adlay (Qiao et al., ). Oncorhynchus mykiss is a marine fish, and it was highly domesticated, fast‐growing, and an attractive food protein source (Hauge et al., ; Leung et al., ).…”

“…. prolyl endopeptidase inhibitors from meat (Lafarga, O'Connor, & Hayes, 2015), antioxidative collagen peptides from carp swim bladder (Roy, Nair, Sen, Soni, & Madhusudhan, 2017), and antihypertensive oligopeptides from adlay (Qiao et al, 2016). Oncorhynchus mykiss is a marine fish, and it was highly domesticated, fast-growing, and an attractive food protein source (Hauge et al, 2017;Leung et al, 2012).…”

ADME Profiling in Drug Discovery and a New Path Paved on Silica

“…While such a broad spectrum of molecule classes offers also a wide range of treatments, at the same time, it exacerbates the need for new developments since every molecule type exhibits different properties. In the field of predicting the biologics activity against specific targets, classical modeling tools, such as Monte Carlo sampling, genetic algorithms, docking, and molecular dynamics simulation, were adapted or even developed anew to accommodate the specifics (as extensively reviewed by [146,147]).…”