Publications de Paolo Carloni | EPFL Graph Search

Sequence-dependent structural properties of B-DNA: what have we learned in 40 years?

John Maddocks, Daiva Petkeviciute, Paolo Carloni, Marco Pasi, Rahul Sharma

The structure of B-DNA, the physiological form of the DNA molecule, has been a central topic in biology, chemistry and physics. Far from uniform and rigid, the double helix was revealed as a flexible and structurally polymorphic molecule. Conformational ch ...

Springernature2021

Accuracy of Molecular Simulation-Based Predictions of k(off) Values: A Metadynamics Study

Ursula Röthlisberger, Michele Parrinello, Paolo Carloni, Simone Meloni, Viacheslav Bolnykh

The k(off) values of ligands unbinding to proteins are key parameters for drug discovery. Their predictions based on molecular simulation may under- or overestimate experiment in a system- and/or technique-dependent way. Here we use an established method-i ...

AMER CHEMICAL SOC2020

Biomolecular Simulation: a Perspective from High Performance Computing

Ursula Röthlisberger, Paolo Carloni, Viacheslav Bolnykh

High-Performance Computing is impacting on all biomedical sciences, including molecular biophysics. Here, we describe general parallel computing strategies (multi-threading and distributed computing) used in all the natural sciences, including molecular bi ...

WILEY-V C H VERLAG GMBH2020

Molecular Basis of CLC Antiporter Inhibition by Fluoride

Ursula Röthlisberger, Paolo Carloni, Thomas Beck, Simone Meloni, Viacheslav Bolnykh

CLC channels and transporters conduct or transport various kinds of anions, with the exception of fluoride, which acts as an effective inhibitor. Here, we performed sub-nanosecond DFT-based QM/MM simulations of the E. coli anion/proton exchanger ClC-ec1 an ...

AMER CHEMICAL SOC2020

MiMiC: Multiscale Modeling in Computational Chemistry

Ursula Röthlisberger, Paolo Carloni, Simone Meloni, Martin Peter Bircher, Viacheslav Bolnykh

FRONTIERS MEDIA SA2020

Regulation of adenylyl cyclase 5 in striatal neurons confers the ability to detect coincident neuromodulatory signals

Ursula Röthlisberger, Paolo Carloni, Siri Camee van Keulen, Daniele Narzi

Author summary Adenylyl cyclases (ACs) are enzymes that can translate extracellular signals into the intracellular molecule cAMP, which is thus a 2nd messenger of extracellular events. The brain expresses nine membrane-bound AC variants, and AC5 is the dom ...

2019

MiMiC: A Novel Framework for Multiscale Modeling in Computational Chemistry

Ursula Röthlisberger, Paolo Carloni, Simone Meloni, Martin Peter Bircher, Viacheslav Bolnykh

We present a flexible and efficient framework for multiscale modeling in computational chemistry (MiMiC). It is based on a multiple-program multiple-data (MPMD) model with loosely coupled programs. Fast data exchange between programs is achieved through th ...

AMER CHEMICAL SOC2019

Extreme Scalability of DFT-Based QM/MM MD Simulations Using MiMiC

Ursula Röthlisberger, Paolo Carloni, Simone Meloni, Martin Peter Bircher, Jógvan Magnus Olsen, Viacheslav Bolnykh

We present a highly scalable DFT-based QM/MM implementation developed within MiMiC, a recently introduced multiscale modeling framework that uses a loose-coupling strategy in conjunction with a multiple-program multiple-data (MPMD) approach. The computatio ...

2019

On the active site of mononuclear B1 metallo beta-lactamases: a computational study

Matteo Dal Peraro, Paolo Carloni

Metallo-beta-lactamases (M beta Ls) are Zn(II)-based bacterial enzymes that hydrolyze beta-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from point to either two zinc ...

2012

Coordination Numbers of K+ and Na+ Ions Inside the Selectivity Filter of the KcsA Potassium Channel: Insights from First Principles Molecular Dynamics

Denis Bucher, Ursula Röthlisberger, Leonardo Guidoni, Paolo Carloni

Quantum mechanics/molecular mechanics (QM/MM) Car-Parrinello simulations were performed to estimate the coordination numbers of K+ and Na+ ions in the selectivity filter of the KcsA channel, and in water. At the DFT/BLYP level, K+ ions were found to displa ...

Elsevier2010

Multi-scale modeling of HIV-1 proteins

Marilisa Neri, Paolo Carloni

The efficiency of protease inhibiting drugs is hampered by the rapid emergence of protease variants. Understanding this phenomenon requires the characterization of the salient steps of HIV-1 protease's catalytic cycle. We summarize Our investigations on th ...

2009

Common mechanistic features among metallo-β-lactamases: a computational study of Aeromonas hydrophila CphA enzyme

Matteo Dal Peraro, Paolo Carloni, Andrea Cavalli

Metallo-β-lactamases (MβLs) constitute an increasingly serious clinical threat by giving rise to β-lactam antibiotic resistance. They accommodate in their catalytic pocket one or two zinc ions, which are responsible for the hydrolysis of β-lactams. Recent ...

2009

Topologically based multipolar reconstruction of electrostatic interactions in multiscale simulations of proteins

Michele Cascella, Matteo Dal Peraro, Paolo Carloni

We present a new method to incorporate electrostatic interactions in coarse-grained representations of proteins. The model is based on a topologically reconstructed multipolar expansion of the all-atom centers of charge, specifically of the backbone dipole ...

2008

Role of protein frame and solvent for the redox properties of azurin from Pseudomonas Aeruginosa

Ursula Röthlisberger, Ivano Tavernelli, Michele Cascella, Paolo Carloni

National Academy of Sciences2006

Duocarmycins binding to DNA explored by Molecular Simulation

Ursula Röthlisberger, Paolo Carloni

2006

Evolutionarily Conserved Functional Mechanics across Pepsin-like and Retroviral Aspartic Proteases

Ursula Röthlisberger, Michele Cascella, Paolo Carloni

The biol. function of the aspartic protease from HIV-1 has recently been related to the conformational flexibility of its structural scaffold. Here, we use a multistep strategy to investigate whether the same mechanism affects the functionality in the peps ...

2005

Duocarmycins binding to DNA explored by molecular simulation

Ursula Röthlisberger, Paolo Carloni

Duocarmycins are a potent class of antitumor agents. Their activity arises by their covalent binding to adenine nucleobases of DNA. We use classical mol. dynamics and hybrid (QM/MM) Car-Parrinello mol. dynamics simulations to study non-covalent and covalen ...

2005