Gaspar P. Pinto

Gaspar P. Pinto
Uppsala University | UU · Department of Chemistry - BMC

PhD in Computational Chemistry

About

28
Publications
5,599
Reads
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374
Citations
Additional affiliations
January 2018 - present
Masaryk University
Position
  • Researcher
April 2017 - present
St. Ann's University Hospital Brno
Position
  • PostDoc Position
January 2016 - December 2016
University of Porto
Position
  • PhD Student
Education
October 2009 - November 2011
University of Porto
Field of study
  • Chemistry

Publications

Publications (28)
Article
Full-text available
The transplantation of loops between structurally related proteins is a compelling method to improve the activity, specificity and stability of enzymes. However, despite the interest of loop regions in protein engineering, the available methods of loop-based rational protein design are scarce. One particular difficulty related to loop engineering i...
Preprint
The widely used coelenterazine-powered Renilla luciferase was discovered over 40 years ago but the oxidative mechanism by which it generates blue photons remains unclear. Here we decipher Renilla-type bioluminescence through crystallographic, spectroscopic, and computational experiments. Structures of ancestral and extant luciferases complexed with...
Article
In the process of understanding and redesigning the function of proteins in modern biochemistry, protein engineers are increasingly focusing on the exploration of regions in proteins called loops. Analyzing various characteristics of these regions helps the experts to design the transfer of the desired function from one protein to another. This pro...
Article
Full-text available
Recent years have seen an explosion of interest in understanding the physicochemical parameters that shape enzyme evolution, as well as substantial advances in computational enzyme design. This review discusses three areas where evolutionary information can be used as part of the design process: (i) using ancestral sequence reconstruction (ASR) to...
Article
The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules appro...
Article
Full-text available
Protein dynamics are often invoked in explanations of enzyme catalysis, but their design has proven elusive. Here we track the role of dynamics in evolution, starting from the evolvable and thermostable ancestral protein Anc HLD-RLuc which catalyses both dehalogenase and luciferase reactions. Insertion-deletion (InDel) backbone mutagenesis of Anc H...
Article
Full-text available
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pathological pulmonary symptoms. Most efforts to develop vaccines and drugs against this virus target the spike glycoprotein, particularly its S1 subunit, which is recognised by angiotensin-converting enzyme 2. Here we use the in-house developed tool CaverDock to perform vi...
Preprint
Full-text available
The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules appro...
Article
Enzymes are the natural catalysts that execute biochemical reactions upholding life. Their natural effectiveness has been fine-tuned as a result of millions of years of natural evolution. Such catalytic effectiveness has prompted the use of biocatalysts from multiple sources on different applications, including the industrial production of goods (f...
Preprint
Full-text available
The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes pathological pulmonary symptoms. Most efforts to develop vaccines and drugs against this virus target the spike glycoprotein, particularly its S1 subunit, which is recognised by angiotensin-converting enzyme 2. Here we use the in-house developed tool CaverDock to perform vi...
Preprint
Full-text available
p>Insertion-deletion mutations are sources of major functional innovations in naturally evolved proteins, but directed evolution methods rely primarily on substitutions. Here, we report a powerful strategy for engineering backbone dynamics based on InDel mutagenesis of a stable and evolvable template, and its validation in application to a thermost...
Article
Full-text available
Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numero...
Article
Full-text available
Transport of ligands between bulk solvent and the buried active sites is a critical event in the catalytic cycle of many enzymes. The rational design of transport pathways is far from trivial due to the lack of knowledge about the effect of mutations on ligand transport. The main and an auxiliary tunnel of haloalkane dehalogenase LinB have been pre...
Article
Full-text available
Protein tunnels and channels are attractive targets for drug design. Drug molecules that block the access of substrates or release of products can be efficient modulators of biological activity. Here, we demonstrate the applicability of a newly developed software tool CaverDock for screening databases of drugs against pharmacologically relevant tar...
Article
Full-text available
Protein tunnels and channels are attractive targets for drug design. Drug molecules that block the access of substrates or release of products can be efficient modulators of biological activity. Here, we demonstrate the applicability of a newly developed software tool CaverDock for screening databases of drugs against pharmacologically relevant tar...
Article
Full-text available
Caver Web 1.0 is a web server for comprehensive analysis of protein tunnels and channels, and study of the ligands' transport through these transport pathways. Caver Web is the first interactive tool allowing both the analyses within a single graphical user interface. The server is built on top of the abundantly used tunnel detection tool Caver 3.0...
Article
Full-text available
To obtain structural insights into the emergence of biological functions from catalytically promiscuous enzymes, we reconstructed an ancestor of catalytically distinct, but evolutionarily related, haloalkane dehalogenases (EC 3.8.1.5) and Renilla luciferase (EC 1.13.12.5). This ancestor has both hydrolase and monooxygenase activities. Crystal struc...
Article
Enzymes are efficient and specific catalysts for many essential reactions in biotechnological and pharmaceutical industries. Many times, the natural enzymes do not display the catalytic efficiency, stability or specificity required for these industrial processes. The current enzyme engineering methods offer solutions to this problem, but they mainl...
Article
Full-text available
Organophosphate degrading enzyme from Agrobacterium radiobacter P230 exhibits promiscuity, not only in the reactions it catalyses, but also in the metals it uses to catalyse those reactions. Here, we studied three different binuclear metal centres, di-Cd(II), di-Mn(II) and Zn(II)-Fe(II), that enzyme can use for hydrolysing trimethyl- and dimethyl-p...
Article
Starch is the most common carbohydrate in human diet consisting of a large chain of glucose units. A wide range of enzymes, called α-amylases, catalyze the hydrolysis of starch to yield lower molecular weight sugars, by cleaving the α(1-4) glycosidic linkages. The human being has two different amylases, one in the saliva (HAS) and the other in the...
Article
The reaction mechanism for the hydrolysis of trimethyl phosphate and of the obtained phosphodiester by the di-CoII derivative of organophosphate degrading enzyme from Agrobacterium radiobacter P230(OpdA), have been investigated at density functional level of theory in the framework of the cluster model approach. Both mechanisms proceed by a multist...
Article
Full-text available
In this study, a set of 50 transition-metal complexes of Cu(I) and Cu(II), were used in the evaluation of 18 density functionals in geometry determination. In addition, 14 different basis sets were considered, including four commonly used Pople's all-electron basis sets; four basis sets including popular types of effective-core potentials: Los Alam...

Questions

Question (1)
Question
I am trying to find if two proteins interact to form an hetero dimer. Is there any software that will predict this?

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Projects

Projects (2)
Project
CaverDock is a software tool for rapid analysis of transport processes in proteins. It models the transportation of a ligand - a substrate, a product, an inhibitor, a co-factor or a co-solvent - from outside environment into the protein active or binding site and vice versa. The tool uses a novel method of continuous ligand trajectory sampling, based on constrained molecular docking. The tool is much faster than molecular dynamic simulations (2-20 min per job), making it suitable even for virtual screening. The first version of the software is available at https://loschmidt.chemi.muni.cz/caverdock/