Affiliation: University of Cambridge
- Chia S, Habchi J, Michaels T, Cohen S, Linse S, Dobson C, et al. SAR by kinetics for drug discovery in protein misfolding diseases. Proc Natl Acad Sci U S A. 2018;115:10245-10250 pubmed publisher..These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers. ..
- Tomba G, Camilloni C, Vendruscolo M. Determination of the conformational states of strychnine in solution using NMR residual dipolar couplings in a tensor-free approach. Methods. 2018;148:4-8 pubmed publisher..We illustrate the method in the case of strychnine, determining the three major conformational states of this small molecule and their associated occupation probabilities. ..
- Cavalli A, Vendruscolo M. Analysis of the performance of the CHESHIRE and YAPP methods at CASD-NMR round 3. J Biomol NMR. 2015;62:503-9 pubmed publisher..6 Ã…. Taken together, these results illustrate how the NOESY based YAPP method and the chemical shift based CHESHIRE method can provide structures of comparable quality. ..
- Kukić P, Alvin Leung H, Bemporad F, Aprile F, Kumita J, De Simone A, et al. Structure and dynamics of the integrin LFA-1 I-domain in the inactive state underlie its inside-out/outside-in signaling and allosteric mechanisms. Structure. 2015;23:745-53 pubmed publisher..These results suggest that the presence of three substates in the apo I-domain enables the precise regulation of the binding process that is essential for the physiological function of LFA-1. ..
- Ciryam P, Kundra R, Morimoto R, Dobson C, Vendruscolo M. Supersaturation is a major driving force for protein aggregation in neurodegenerative diseases. Trends Pharmacol Sci. 2015;36:72-7 pubmed publisher..These observations suggest that effective therapeutic approaches designed to combat neurodegenerative diseases could be aimed at enhancing the ability of the cell to maintain the homeostasis of the metastable subproteome. ..
- Joshi P, Vendruscolo M. Druggability of Intrinsically Disordered Proteins. Adv Exp Med Biol. 2015;870:383-400 pubmed publisher..By analysing the results of recent studies, we describe the main structural features that may render IDPs druggable, and describe techniques that can be used for drug discovery programs focused on IDPs. ..
- Sormanni P, Aprile F, Vendruscolo M. Rational design of antibodies targeting specific epitopes within intrinsically disordered proteins. Proc Natl Acad Sci U S A. 2015;112:9902-7 pubmed publisher..Taken together, these results indicate that the design strategy that we propose makes it possible to obtain antibodies targeting given epitopes in disordered proteins or protein regions. ..
- Borkar A, Bardaro M, Camilloni C, Aprile F, Varani G, Vendruscolo M. Structure of a low-population binding intermediate in protein-RNA recognition. Proc Natl Acad Sci U S A. 2016;113:7171-6 pubmed publisher..These results identify the structure of an intermediate for RNA-protein binding and illustrate a general strategy to achieve this goal with high resolution. ..
- Ciryam P, Kundra R, Freer R, Morimoto R, Dobson C, Vendruscolo M. A transcriptional signature of Alzheimer's disease is associated with a metastable subproteome at risk for aggregation. Proc Natl Acad Sci U S A. 2016;113:4753-8 pubmed publisher..These results suggest that the down-regulation of a metastable subproteome may help mitigate aberrant protein aggregation when protein homeostasis becomes compromised in Alzheimer's disease. ..
- Perni M, Challa P, Kirkegaard J, Limbocker R, Koopman M, Hardenberg M, et al. Massively parallel C. elegans tracking provides multi-dimensional fingerprints for phenotypic discovery. J Neurosci Methods. 2018;306:57-67 pubmed publisher..We anticipate that this approach will further extend the scope and utility of C. elegans as a model organism. ..
- Heller G, Aprile F, Vendruscolo M. Methods of probing the interactions between small molecules and disordered proteins. Cell Mol Life Sci. 2017;74:3225-3243 pubmed publisher..In discussing these techniques, we also point out directions for future developments. ..
- Perni M, Aprile F, Casford S, Mannini B, Sormanni P, Dobson C, et al. Delivery of Native Proteins into C. elegans Using a Transduction Protocol Based on Lipid Vesicles. Sci Rep. 2017;7:15045 pubmed publisher..elegans model of Parkinson's disease. As this transduction protocol is fast and inexpensive, we anticipate that it will be readily applicable to protein-based drug discovery studies that utilize C. elegans as a model organism. ..
- Heller G, Aprile F, Bonomi M, Camilloni C, De Simone A, Vendruscolo M. Sequence Specificity in the Entropy-Driven Binding of a Small Molecule and a Disordered Peptide. J Mol Biol. 2017;429:2772-2779 pubmed publisher..These results suggest that the binding mechanism that we report may create novel opportunities to discover drugs that target disordered proteins in their monomeric states in a specific manner. ..
- Chia S, Flagmeier P, Habchi J, Lattanzi V, Linse S, Dobson C, et al. Monomeric and fibrillar α-synuclein exert opposite effects on the catalytic cycle that promotes the proliferation of Aβ42 aggregates. Proc Natl Acad Sci U S A. 2017;114:8005-8010 pubmed publisher..It is thus the specific balance between the concentrations of monomeric and fibrillar α-synuclein that determines the outcome of the Aβ42 aggregation reaction. ..