Complex peptide macrocycle optimization: combining NMR restraints with conformational analysis to guide structure-based and ligand-based design

AN Jain, AC Brueckner, C Jorge, AE Cleves… - Journal of Computer …, 2023 - Springer
Systematic optimization of large macrocyclic peptide ligands is a serious challenge. Here,
we describe an approach for lead-optimization using the PD-1/PD-L1 system as a …

Complex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen

AN Jain, AE Cleves, Q Gao, X Wang, Y Liu… - Journal of computer …, 2019 - Springer
ForceGen is a template-free, non-stochastic approach for 2D to 3D structure generation and
conformational elaboration for small molecules, including both non-macrocycles and …

Conformational Strain of Macrocyclic Peptides in Ligand–Receptor Complexes Based on Advanced Refinement of Bound-State Conformers

AC Brueckner, Q Deng, AE Cleves… - Journal of Medicinal …, 2021 - ACS Publications
Macrocyclic peptides are an important modality in drug discovery, but molecular design is
limited due to the complexity of their conformational landscape. To better understand …

Comprehensive computational design of ordered peptide macrocycles

P Hosseinzadeh, G Bhardwaj, VK Mulligan… - Science, 2017 - science.org
Mixed-chirality peptide macrocycles such as cyclosporine are among the most potent
therapeutics identified to date, but there is currently no way to systematically search the …

Structure-based integrative computational and experimental approach for the optimization of drug design

D Morikis, CA Floudas, JD Lambris - … , Atlanta, GA, USA, May 22-25, 2005 …, 2005 - Springer
We present an integrative approach for the optimization in the design of peptides which are
candidates to become therapeutic agents. This approach is based on the structure of the …

The emerging role of computational design in peptide macrocycle drug discovery

VK Mulligan - Expert Opinion on Drug Discovery, 2020 - Taylor & Francis
Drug discovery is a laborious process with rising cost per new drug. Peptide macrocycles
are promising therapeutics, though conformational flexibility can reduce target affinity and …

Cyclic peptide linker design and optimization by molecular dynamics simulations

L Yu, SA Barros, C Sun, S Somani - Journal of Chemical …, 2023 - ACS Publications
Cyclic peptides are an emerging therapeutic modality that can target protein–protein
interaction sites with high affinity and selectivity. A common medicinal chemistry strategy for …

Computational generation of an annotated gigalibrary of synthesizable, composite peptidic macrocycles

I Saha, EK Dang, D Svatunek… - Proceedings of the …, 2020 - National Acad Sciences
Peptidomimetic macrocycles have the potential to regulate challenging therapeutic targets.
Structures of this type having precise shapes and drug-like character are particularly …

[HTML][HTML] Macrocyclic peptidomimetics-forcing peptides into bioactive conformations

DP Fairlie, G Abbenante… - Current medicinal …, 1995 - books.google.com
Cyclic peptides that are potent regulators of biological processes are rapidly emerging as
important mechanistic probes and drug leads. Nature clearly uses macrocycles to, constrain …

Using 1 H and 13 C NMR chemical shifts to determine cyclic peptide conformations: a combined molecular dynamics and quantum mechanics approach

QNN Nguyen, J Schwochert, DJ Tantillo… - Physical Chemistry …, 2018 - pubs.rsc.org
Solving conformations of cyclic peptides can provide insight into structure–activity and
structure–property relationships, which can help in the design of compounds with improved …