ArticleProteins2011
Design of a modified mouse protein with ligand binding properties of its human analog by molecular dynamics simulations: the case of C3 inhibition by compstatin.
Article in Proteins, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Using genetics to explore complement C5 as a druggable protein in periodontitis.Frontiers in immunology · 2024Pooled it
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- Interactions between Curcumin Derivatives and Amyloid-β Fibrils: Insights from Molecular Dynamics Simulations.Journal of chemical information and modeling · 2020Article
- Molecular Mechanism for Attractant Signaling to DHMA by E. coli Tsr.Biophysical journal · 2020Article
- Computational evolution of an RNA-binding protein towards enhanced oxidized-RNA binding.Computational and structural biotechnology journal · 2020Article
- Elucidating the multi-targeted anti-amyloid activity and enhanced islet amyloid polypeptide binding ofComputers & chemical engineering · 2018Article
- Article
- Editor's Highlight: Microbial-Derived 1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon Receptor Agonists/Antagonists: Structure-Activity Relationships and Receptor Modeling.Toxicological sciences : an official journal of the Society of Toxicology · 2017Article
- Insights from molecular dynamics simulations for computational protein design.Molecular systems design & engineering · 2017Article
- N-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils.Infection and immunity · 2016Article
- Forcefield_NCAA: ab initio charge parameters to aid in the discovery and design of therapeutic proteins and peptides with unnatural amino acids and their application to complement inhibitors of the compstatin family.ACS synthetic biology · 2014Article
- Elucidating a key anti-HIV-1 and cancer-associated axis: the structure of CCL5 (Rantes) in complex with CCR5.Scientific reports · 2014Article
- Elucidating a key component of cancer metastasis: CXCL12 (SDF-1α) binding to CXCR4.Journal of chemical information and modeling · 2014Article
- Insights into the mechanism of C5aR inhibition by PMX53 via implicit solvent molecular dynamics simulations and docking.BMC biophysics · 2014Article
- Molecular recognition of CCR5 by an HIV-1 gp120 V3 loop.PloS one · 2014Article
- Novel compstatin family peptides inhibit complement activation by drusen-like deposits in human retinal pigmented epithelial cell cultures.Experimental eye research · 2013Article
- Molecular recognition of CXCR4 by a dual tropic HIV-1 gp120 V3 loop.Biophysical journal · 2013Article
- Molecular dynamics in drug design: new generations of compstatin analogs.Chemical biology & drug design · 2012Article
- Insights into the structure, correlated motions, and electrostatic properties of two HIV-1 gp120 V3 loops.PloS one · 2012Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The peptide compstatin and its derivatives inhibit the complement-component protein C3 in primate mammals and are potential therapeutic agents against the unregulated activation of complement in humans, but are inactive against C3 from lower mammals. Recent molecular dynamics (MD) simulations showed that the most potent compstatin analog comprised entirely of natural amino acids (W4A9) had a smaller affinity for rat C3, due to reproducible changes in the rat protein structure with respect to the human protein, which eliminated or weakened specific protein-ligand interactions seen in the human C3:W4A9 complex. Here, we study by MD simulations three W4A9 complexes with the mouse C3 protein, and two "transgenic" mouse derivatives, containing a small number (6-9) of human C3 substitutions. The mouse complex experiences the conformational changes and affinity reduction of the rat complex. In the "transgenic" complexes, the conformation remains closer to that of the human complex, the protein-ligand interactions are improved, and the affinity for compstatin becomes "human-like." The present work creates new avenues for a compstatin-sensitive animal model. A similar strategy, involving the comparison of a series of complexes by MD simulations, could be used to design "transgenic" sequences in other systems.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.