Adolfo Poma Bernaola, Ph.D.

Department of Biosystems and Soft Matter (ZBiMM)
Division of Modelling in Biology and Medicine (PMBM)
position: assistant professor
telephone: (+48) 22 826 12 81 ext.: 225
room: 225
e-mail: apoma

Doctoral thesis
2011-05-09Coarse-graining and quantum-classical adaptive coupling in soft matter 
supervisor -- Prof. Kremer Kurt, Ph.D., Max Planck IfPR
supervisor -- Prof. Luigi Delle-Site, Ph.D., Max Planck IfPR
1389
 
Recent publications
1.Poma Bernaola A., Li M.S., Theodorakis P.E., Generalization of the elastic network model for the study of large conformational changes in biomolecules, Physical Chemistry Chemical Physics, ISSN: 1463-9076, DOI: 10.1039/C8CP03086C, Vol.20, pp.17020-17028, 2018
Abstract:

The elastic network (EN) is a prime model that describes the long-time dynamics of biomolecules. However, the use of harmonic potentials renders this model insufficient for studying large conformational changes of proteins (e.g. stretching of proteins, folding and thermal unfolding). Here, we extend the capabilities of the EN model by using a harmonic approximation described by Lennard-Jones (LJ) interactions for far contacts and native contacts obtained from the standard overlap criterion as in the case of Gō-like models. While our model is validated against the EN model by reproducing the equilibrium properties for a number of proteins, we also show that the model is suitable for the study of large conformation changes by providing various examples. In particular, this is illustrated on the basis of pulling simulations that predict with high accuracy the experimental data on the rupture force of the studied proteins. Furthermore, in the case of DDFLN4 protein, our pulling simulations highlight the advantages of our model with respect to Gō-like approaches, where the latter fail to reproduce previous results obtained by all-atom simulations that predict an additional characteristic peak for this protein. In addition, folding simulations of small peptides yield different folding times for α-helix and β-hairpin, in agreement with experiment, in this way providing further opportunities for the application of our model in studying large conformational changes of proteins. In contrast to the EN model, our model is suitable for both normal mode analysis and molecular dynamics simulation. We anticipate that the proposed model will find applications in a broad range of problems in biology, including, among others, protein folding and thermal unfolding.

Keywords:

Free Energy, protein, elastic network, molecular dynamics, normal mode analysis

Affiliations:
Poma Bernaola A.-other affiliation
Li M.S.-Institute of Physics, Polish Academy of Sciences (PL)
Theodorakis P.E.-Institute of Physics, Polish Academy of Sciences (PL)
2.Poma Bernaola A., Chwastyk M., Cieplak M., Elastic moduli of biological fibers in a coarse-grained model: crystalline cellulose and β-amyloids, Physical Chemistry Chemical Physics, ISSN: 1463-9076, DOI: 10.1039/C7CP05269C, Vol.19, pp.28195-28206, 2017
Abstract:

We study the mechanical response of cellulose and β-amyloid microfibrils to three types of deformation: tensile, indentational, and shear. The cellulose microfibrils correspond to the allomorphs Iα or Iβ whereas the β-amyloid microfibrils correspond to the polymorphs of either two- or three-fold symmetry. This response can be characterized by three elastic moduli, namely, YL, YT, and S. We use a structure-based coarse-grained model to analyze the deformations in a unified manner. We find that each of the moduli is almost the same for the two allomorphs of cellulose but YL is about 20 times larger than YT (140 GPa vs. 7 GPa), indicating the existence of significant anisotropy. For cellulose we note that the anisotropy results from the involvement of covalent bonds in stretching. For β-amyloid, the sense of anisotropy is opposite to that of cellulose. In the three-fold symmetry case, YL is about half of YT (3 vs. 7) whereas for two-fold symmetry the anisotropy is much larger (1.6 vs. 21 GPa). The S modulus is derived to be 1.2 GPa for three-fold symmetry and one half of it for the other symmetry and 3.0 GPa for cellulose. The values of the moduli reflect deformations in the hydrogen-bond network. Unlike in our theoretical approach, no experiment can measure all three elastic moduli with the same apparatus. However, our theoretical results are consistent with various measured values: typical YL for cellulose Iβ ranges from 133 to 155 GPa, YT from 2 to 25 GPa, and S from 1.8 to 3.8 GPa. For β-amyloid, the experimental values of S and YT are about 0.3 GPa and 3.3 GPa respectively, while the value of YL has not been reported.

Keywords:

Tensile, shear, indentation, Atomic Force Microscopy, amyloid, cellulose

Affiliations:
Poma Bernaola A.-other affiliation
Chwastyk M.-Institute of Physics, Polish Academy of Sciences (PL)
Cieplak M.-Institute of Physics, Polish Academy of Sciences (PL)
3.Poma Bernaola A., Cieplak M., Theodorakis P.E., Combining the MARTINI and Structure-Based Coarse-Grained Approaches for the Molecular Dynamics Studies of Conformational Transitions in Proteins, Journal of Chemical Theory and Computation, ISSN: 1549-9618, DOI: 10.1021/acs.jctc.6b00986, Vol.13, pp.1366-1374, 2017
Abstract:

The application of coarse-grained (CG) models in biology is essential to access large length and time scales required for the description of many biological processes. The ELNEDIN protein model is based on the well-known MARTINI CG force-field and incorporates additionally harmonic bonds of a certain spring constant within a defined cutoff distance between pairs of residues, in order to preserve the native structure of the protein. In this case, the use of unbreakable harmonic bonds hinders the study of unfolding and folding processes. To overcome this barrier we have replaced the harmonic bonds with Lennard–Jones interactions based on the contact map of the native protein structure as is done in Go̅-like models. This model exhibits very good agreement with all-atom simulations and the ELNEDIN. Moreover, it can capture the structural motion linked to particular catalytic activity in the Man5B protein, in agreement with all-atom simulations. In addition, our model is based on the van der Waals radii, instead of a cutoff distance, which results in a smaller contact map. In conclusion, we anticipate that our model will provide further possibilities for studying biological systems based on the MARTINI CG force-field by using advanced-sampling methods, such as parallel tempering and metadynamics.

Keywords:

Martini force field, protein, molecular simulation, stretching AFM, large conformational changes

Affiliations:
Poma Bernaola A.-other affiliation
Cieplak M.-Institute of Physics, Polish Academy of Sciences (PL)
Theodorakis P.E.-Institute of Physics, Polish Academy of Sciences (PL)
4.Poma Bernaola A., Chwastyk M., Cieplak M., Coarse-grained model of the native cellulose and the transformation pathways to the allomorph, CELLULOSE, ISSN: 0969-0239, DOI: 10.1007/s10570-016-0903-4, Vol.23, pp.1573-1591, 2016
Abstract:

All-atom simulations are used to derive effective parameters for a coarse-grained description of the crystalline cellulose I

Keywords:

Cellulose, microfibril, allomorphs, structural transition, molecular dynamics, free energy

Affiliations:
Poma Bernaola A.-other affiliation
Chwastyk M.-Institute of Physics, Polish Academy of Sciences (PL)
Cieplak M.-Institute of Physics, Polish Academy of Sciences (PL)
5.Poma Bernaola A., Chwastyk M., Cieplak M., Polysaccharide–protein complexes in a Coarse-Grained Model, JOURNAL OF PHYSICAL CHEMISTRY B, ISSN: 1520-6106, DOI: 10.1021/acs.jpcb.5b06141, Vol.119, pp.12028-12041, 2015
Abstract:

We construct two variants of coarse-grained models of three hexaoses: one based on the centers of mass of the monomers and the other associated with the C4 atoms. The latter is found to be better defined and more suitable for studying interactions with proteins described within α-C based models. We determine the corresponding effective stiffness constants through all-atom simulations and two statistical methods. One method is the Boltzmann inversion (BI) and the other, named energy-based (EB), involves direct monitoring of energies as a function of the variables that define the stiffness potentials. The two methods are generally consistent in their account of the stiffness. We find that the elastic constants differ between the hexaoses and are noticeably different from those determined for the crystalline cellulose Iβ. The nonbonded couplings through hydrogen bonds between different sugar molecules are modeled by the Lennard-Jones potentials and are found to be stronger than the hydrogen bonds in proteins. We observe that the EB method agrees with other theoretical and experimental determinations of the nonbonded parameters much better than BI. We then consider the hexaose-Man5B catalytic complexes and determine the contact energies between their the C4−α-C atoms. These interactions are found to be stronger than the proteinic hydrogen bonds: about four times as strong for cellohexaose and two times for mannohexaose. The fluctuational dynamics of the coarse-grained complexes are found to be compatible with previous all-atom studies by Bernardi et al.

Keywords:

Polysaccharide, protein, principal component analysis, coarse graining, molecular simulation

Affiliations:
Poma Bernaola A.-other affiliation
Chwastyk M.-Institute of Physics, Polish Academy of Sciences (PL)
Cieplak M.-Institute of Physics, Polish Academy of Sciences (PL)
6.Chwastyk M., Poma Bernaola A., Cieplak M., Statistical radii associated with amino acids to determine the contact map: fixing the structure of a type I cohesin domain in the Clostridium thermocellum cellulosome, PHYSICAL BIOLOGY, ISSN: 1478-3967, DOI: 10.1088/1478-3975/12/4/046002, Vol.12, No.046002, pp.1-11, 2015
Abstract:

We propose to improve and simplify protein refinement procedures through consideration of which pairs of amino acid residues should form native contacts. We first consider 11 330 proteins from the CATH database to determine statistical distributions of contacts associated with a given type of amino acid. The distributions are set across the distances between the α-C atoms that are in contact. Based on this data, we determine typical radii of effective spheres that can be placed on the α-C atoms in order to reconstruct the distribution of the contact lengths. This is done by checking for overlaps with enlarged van der Waals spheres associated with heavy atoms on other amino acids.The resulting contacts can be used to identify non-native contacts that may arise during the time evolution of structure-based models. Here, the radii are used to guide reconstruction of nine missing side chains in a type I cohesin domain with the Protein Data Bank code 1AOH. We first identify the likely missing contacts and then sculpt the corresponding side chains by standard refinement tools to achieve consistency with the expected contact map. One ambiguity in refinement is resolved by determining all-atom conformational energies.

Keywords:

Cohesin, Go-like model, protein prediction, proteins, AFM, stretching

Affiliations:
Chwastyk M.-Institute of Physics, Polish Academy of Sciences (PL)
Poma Bernaola A.-other affiliation
Cieplak M.-Institute of Physics, Polish Academy of Sciences (PL)
7.Poma Bernaola A., Monteferrante M., Bonella S., Ciccotti G., The quantum free energy barrier for hydrogen vacancy diffusion in Na3AlH6, Physical Chemistry Chemical Physics, ISSN: 1463-9076, DOI: 10.1039/C2CP42536J , Vol.14, pp.15458-15463, 2012
Abstract:

The path integral single sweep method is used to assess quantum effects on the free energy barrier for hydrogen vacancy diffusion in a defective Na3AlH6 crystal. This process has been investigated via experiments and simulations due to its potential relevance in the H release mechanism in sodium alanates, prototypical materials for solid state hydrogen storage. Previous computational studies, which used density functional methods for the electronic structure, were restricted to a classical treatment of the nuclear degrees of freedom. We show that, although they do not change the qualitative picture of the process, nuclear quantum effects reduce the free energy barrier height by about 18% with respect to the classical calculation improving agreement with available neutron scattering data.

Keywords:

Alanate, proton transfer, electron hopping, Car-Parrinello MD, molecular dynamics, Free Energy, Path Integral

Affiliations:
Poma Bernaola A.-other affiliation
Monteferrante M.-Sapienza University of Rome (IT)
Bonella S.-Sapienza University of Rome (IT)
Ciccotti G.-Sapienza University of Rome (IT)
8.Poma Bernaola A., Site Delle L., Classical to Path-Integral Adaptive Resolution in Molecular Simulation: Towards a Smooth Quantum-Classical Coupling, PHYSICAL REVIEW LETTERS, ISSN: 0031-9007, DOI: 10.1103/PhysRevLett.104.250201, Vol.104, pp.250201-1-4, 2011
Abstract:

Simulations that couple different molecular models in an adaptive way by changing resolution on the fly allow us to identify the relevant degrees of freedom of a system. This, in turn, leads to a detailed understanding of the essential physics which characterizes a system. While the delicate process of transition from one model to another is well understood for the adaptivity between classical molecular models the same cannot be said for the quantum-classical adaptivity. The main reason for this is the difficulty in describing a continuous transition between two different kinds of physical principles: probabilistic for the quantum and deterministic for the classical. Here we report the basic principles of an algorithm that allows for a continuous and smooth transition by employing the path integral description of atoms.

Keywords:

path integral, classical-quantum coupling, adaptive resolution scheme, polymer ring, quantum structure

Affiliations:
Poma Bernaola A.-other affiliation
Site Delle L.-Max-Planck-Institute for Polymer Research (DE)
9.Poma Bernaola A., Site Delle L., Adaptive resolution simulation of liquid para-hydrogen: Testing the robustness of the quantum-classical adaptive coupling, Physical Chemistry Chemical Physics, ISSN: 1463-9076, DOI: 10.1039/C0CP02865G , Vol.13, pp.10510-10519, 2011
Abstract:

Adaptive resolution simulations for classical systems are currently made within a reasonably consistent theoretical framework. Recently we have extended this approach to the quantum-classical coupling by mapping the quantum nature of an atom onto a classical polymer ring representation within the path integral approach [Poma & Delle Site, Phys. Rev. Lett., 2010, 104, 250201]. In this way the process of interfacing adaptively a quantum representation to a classical one corresponds to the problem of interfacing two regions with a different number of effective “classical” degrees of freedom; thus the classical formulation of the adaptive algorithm applies straightforwardly to the quantum-classical problem. In this work we show the robustness of such an approach for a liquid of para-hydrogen at low temperature. This system represents a highly challenging conceptual and technical test for the adaptive approach due to the extreme thermodynamical conditions where quantum effects play a central role.

Keywords:

Adaptive resolution Scheme, parahydrogen, path integral, polymer ring, quantum fluid

Affiliations:
Poma Bernaola A.-other affiliation
Site Delle L.-Max-Planck-Institute for Polymer Research (DE)
10.Poma Bernaola A., Site Delle L., Separation of variables in molecular-dynamics simulations: A criterion to estimate the quality of the approximation, PHYSICAL REVIEW E, ISSN: 1539-3755, DOI: 10.1103/PhysRevE.78.056703, Vol.78, pp.056703-1-11, 2008
Abstract:

We propose a simple method to evaluate the approximation of separation of variables in molecular dynamics (MD) and related fields. It is based on a point-by-point evaluation of the difference between the true potential and the corresponding potential where the separation of variables is applied. The major advantage of such an approach is the fact that it requires only the analytical form of the potential as provided in most of the MD codes. We provide two examples of application, namely, a diatomic molecule adsorbing on a flat surface and an alkane (aliphatic) chain.

Keywords:

Quality control, independent DOF, coarse graining, aliphatic chain, intramolecular

Affiliations:
Poma Bernaola A.-other affiliation
Site Delle L.-Max-Planck-Institute for Polymer Research (DE)

Conference abstracts
1.Poma Bernaola A., Theodorakis P.E., Generalization of the Elastic Network Model for the Study of Large Conformational Changes in Proteins, BPS2018, 62nd Annual Meeting of the Biophysical Society, 2018-02-17/02-21, San Francisco (US), DOI: 10.1016/j.bpj.2017.11.306, No.114, pp.46A, 2018
Abstract:

The Elastic Network (EN) is a prime model that describes the long-time dynamics of biomolecules. However, the use of harmonic potentials renders this model insufficient for studying large conformational changes. Here, we propose a model based on the EN, a harmonic approximation described by Lennard-Jones interactions for far contacts, and Go-type native contacts obtained from the standard overlap criterion with the latter describing hydrogen bonds, ionic bridges and hydrophobic/hydrophilic interactions. Our results based on Normal Mode Analysis show excellent agreement with the EN model. Moreover, we apply large forces along the N- and C-termini in order to study a large conformational change (i.e. protein stretching), our pulling simulations reproduce the experimental data on the maximum force of the unfolding of a protein domain. We anticipate that our work will provide new venues for the EN in a broader range of problems in biology, including folding of proteins and protein-docking prediction

Keywords:

Protein, Biomolecules, deformation, AFM, stretching, Normal Modes

Affiliations:
Poma Bernaola A.-other affiliation
Theodorakis P.E.-Institute of Physics, Polish Academy of Sciences (PL)