Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide

Revilla-López, Guillem; Torras, Juan; Nussinov, Ruth; Alemán, Carlos; Zanuy, David

doi:10.1039/c0cp02572k

Cited by 8 publications

(10 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…REMD is a technique used to enhance sampling relative to standard MD simulations by allowing systems of similar potential energies to sample conformations at different temperatures. By applying this procedure, energy barriers on the potential energy surface can be overcome, allowing exploration of different regions of the conformational space . The system, the number of replicas, the range of temperature space, and the distribution of temperatures determine the average exchange probability between each replica.…”

Section: Methodsmentioning

confidence: 99%

“…By applying this procedure, energy barriers on the potential energy surface can be overcome, allowing exploration of different regions of the conformational space. 41 The system, number of replicas, range of temperature space and the distribution of temperatures determine the average exchange probability between each replica. A total of 32 replicas were exponentially distributed from temperatures of 250.0 K up to 380.0 K. Simulations were run in the Barcelona Supercomputer Center's (BSC's) Minotauro GPU cluster using a total amount of 32 GPUs (one per temperature).…”

Section: Replica Exchange Molecular Dynamics Protocolmentioning

confidence: 99%

See 1 more Smart Citation

Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

Martí

Ainsley

Ahumada³

et al. 2020

Langmuir

Self Cite

View full text Add to dashboard Cite

A key factor for improving the sensitivity and performance of immunosensors based on mechanical-plasmonic methods is the orientation of the antibody proteins immobilized on the inorganic surface. Although experimental techniques fail to determine surface phenomena at the molecular level, modern simulations open the possibility of improving our understanding of protein-surface interactions. In this work, Replica Exchange Molecular Dynamics (REMD) simulations have been used to model the IgG1 protein tethered on amorphous silica surface considering a united-atom model and a relatively large system (2500 nm 2 surface). Additional Molecular Dynamics (MD) simulations have been conducted to derive an atomistic model for the amorphous silica surface using the cristobalite crystal structure as starting point and to examine the structure of the free IgG1 antibody in solution for comparison when immobilized. Analyses of the trajectories obtained for the tethered IgG1, which was sampled considering 32 different temperatures, have been used to define the geometry of the protein with respect to the inorganic surface. The tilt angle of the protein with respect to the surface plane increases with the temperature, the most populated value being 24º, and 66º and 87º at the lowest (250 K), room (298 K) and highest (380 K) temperature. This variation indicates that the importance of proteinsurface interactions decreases with increasing temperature. The influence of the surface on the structure of the antibody is very significant in the constant region, which is directly involved in the tethering process, while it is relatively unimportant for the antigen-binding fragments, which are farthest from the surface. These results are expected to contribute to the development of improved mechanical-plasmonic sensor microarrays in the near future.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Replica Exchange Molecular Dynamics Protocolmentioning

confidence: 99%

Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

Martí

Ainsley

Ahumada³

et al. 2020

Langmuir

Self Cite

View full text Add to dashboard Cite

show abstract

“…A special force field parametrization was obtained for R-PLA to better depict the behavior of the ester linkage. 29 Simulations were made in an orthorhombic box of 201 × 143 × 196 Å and 197 × 147 × 197 Å for Neuro and Vas, respectively. The water molecules were represented explicitly and the total number of atoms was 557 943 and 518 550 for the Neuro and Vas conjugates, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…We have chosen an SA protocol for the conformational exploration of the free peptides since this method has proven useful for conformational exploration of peptides in solution . These advantages include the ability of the method to overcome high potential energy barriers and to proficiently explore flat potential energy surfaces compared to plain molecular dynamics (MD) due to its high dependence on the initial geometry . To explore the long-term stability of the lowest energy structures found in the clustering at room temperature (298 K), 20 ns of NVT-MD simulations were later performed by using the 4 lowest energy structures of Neuro and Vas (see Figure ) as starting structures.…”

Section: Methodsmentioning

confidence: 99%

Conformational Exploration of Two Peptides and Their Hybrid Polymer Conjugates: Potentialities As Self-Aggregating Materials

et al. 2012

Self Cite

View full text Add to dashboard Cite

In this work we elucidate the conformational preferences of two amyloid-forming peptides, Arginine-Vasopressin and Neuromedin-K, and two new biomacromolecular conjugates obtained by linking the two peptides to a polyester (poly(R-lactic acid)) chain. The conformational properties of the new hybrid conjugates have been assessed through molecular dynamics simulations and compared to those of their individual components. Our results suggest that the free unconjugated peptides tend to adopt backbone arrangements which resemble a β-hairpin shape, a conformation which has been reported to facilitate amyloid self-aggregation. The backbone conformational preferences of the unlinked peptides are maintained in the peptide-polymer hybrid. Yet significant differences in the side-chains nonbonding interactions patterns were detected between the two states. This suggests that the conformational profile of the peptides' backbones is preserved when linked to the polymer, maintaining the amyloid precursor-like structure. Additionally, several hydrodynamic parameters were computed for both the polylactic acid and for the conjugates: no significant differences were observed, which suggests that the peptide moiety of the hybrid does not significantly affect the conformational tendencies of the polymer chain. Combined, our results provide a conformational exploration of two amyloid-forming peptides and first steps toward the design of two feasible self-aggregating hybrid materials.

show abstract

“…All these criteria were found to be successful for the identification of bioactive clusters in linear peptides. [63][64][65] Table 3 summarizes the main results of the clustering analysis while details about the existing interactions are provided in Table S1 (ESI †).…”

Section: Fourier Transform Infrared (Ftir) Studymentioning

confidence: 99%

Elucidating the mechanism of interaction between peptides and inorganic surfaces

Maity

Zanuy

Razvag

et al. 2015

Phys. Chem. Chem. Phys.

Self Cite

View full text Add to dashboard Cite

Understanding the mechanism of interaction between peptides and inorganic materials is of high importance for the development of new composite materials. Here, we combined an experimental approach along with molecular simulations in order to gain insights into this binding process. Using single molecule force spectroscopy by atomic force microscopy and molecular simulations we studied the binding of a peptide towards an inorganic substrate. By performing alanine scan we examined the propensity of each amino acid in the peptide sequence to bind the substrate (mica). Our results indicate that this binding is not controlled by the specific sequence of the peptide, but rather by its conformational freedom in solution versus its freedom when it is in proximity to the substrate. When the conformational freedom of the peptide is identical in both environments, the peptide will not adhere to the substrate. However, when the conformational freedom is reduced, i.e., when the peptide is in close proximity to the substrate, binding will occur. These results shed light on the interaction between peptides and inorganic materials.

show abstract

Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide

Cited by 8 publications

References 39 publications

Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

Tethering of the IgG1 Antibody to Amorphous Silica for Immunosensor Development: A Molecular Dynamics Study

Conformational Exploration of Two Peptides and Their Hybrid Polymer Conjugates: Potentialities As Self-Aggregating Materials

Elucidating the mechanism of interaction between peptides and inorganic surfaces

Contact Info

Product

Resources

About