From Biomedicinal to In Silico Models and Back to Therapeutics: A Review on the Advancement of Peptidic Modeling

Abstract

Bioactive peptides participate in numerous metabolic functions of living organisms and have emerged as potential therapeutics on a diverse range of diseases. Albeit peptide design does not go without challenges, overwhelming advancements on in silico methodologies have increased the scope of peptide-based drug design and discovery to an unprecedented amount. Within an in silico model versus an experimental validation scenario, this review aims to summarize and discuss how different in silico techniques contribute at present to the design of peptide-based molecules. Published in silico results from 2014 to 2018 were selected and discriminated in major methodological groups, allowing a transversal analysis, promoting a landscape vision and asserting its increasing value in drug design.

Methyl 2-[3-(4-hydroxyphenyl)prop-2-enoylamino]-3-phenylpropanoate Is a Potent Cell-Permeable Anti-Cytokine Compound To Inhibit Inflammatory Cytokines in Monocyte/Macrophage-Like Cells

“…inflammatory cytokines, especially IL-6 (Park, 2017;Allen and Geldenhuys 2006;Moura et al, 2019;Chakraborty et al, 2020;Szollosi et al, 2018).…”

“…Then, the effects of MHPAP on MAPK and NF-κB signal pathways were investigated in the THP-1 cells, because these two signal pathways are significantly involved in the production of inflammatory cytokines in the cells (Awasthi et al, 2021;Gadina et al, 2017;Ahmed et al, 2015;Lawrence, 2009;Yeung et al, 2018). In silico molecular analysis was also conducted to identify a potential binding site for MHPAP in a candidate molecule in the signal pathway, because the molecular modeling has been used for years to identify potential inhibitors for targeted molecules (Park, 2017;Allen and Geldenhuys 2006;Moura et al, 2019).…”

Biosensing materials for monoclonal antibody detection: An overview

“…[63,64,66,73] Mimotopes can also be prepared using fragment structure or sequence information from the region in which the antigen binds to the mAb; the mimotopes yield detailed binding information. [74] Methods have been developed to predict conformational epitopes in antigens based on the antigen sequence (CBtope) or antigen structure (DiscoTope, BEpro, etc.). [75] Zhang et al used the crystal complex structure of the cetuximab-epidermal growth factor receptor extracellular domain to rationalize the design of peptide mimetics that exhibited high affinity and specific binding.…”

“…Approximately 15 years ago, peptide sequences specifically recognizing certain mAbs, such as trastuzumab, cetuximab, and rituximab, were successively screened by Ph.D.; similarity was demonstrated between the peptides and the epitopes recognized by the mAbs (Table 3). [63,64,66,73] Mimotopes can also be prepared using fragment structure or sequence information from the region in which the antigen binds to the mAb; the mimotopes yield detailed binding information [74] . Methods have been developed to predict conformational epitopes in antigens based on the antigen sequence (CBtope) or antigen structure (DiscoTope, BEpro, etc.)…”

Predicting the Surface Tension of Deep Eutectic Solvents: A Step Forward in the Use of Greener Solvents

“…The question that yet remains is whether a more predictive model for the surface tension of DESs can be achieved by alternative in silico-based modeling approaches such as the one proposed here, Quantitative Structure-Property Relationships (QSPR). In fact, the application of QSPR modeling techniques has long stood as particularly useful to estimate a wide range of properties of different materials [ 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Thus, many QSPR modeling studies have been devoted to different physicochemical properties of DESs.…”