Energy Component Analysis Research Articles

Energy Component Analysis for Electronically Excited States of Molecules: Why the Lowest Excited State Is Not Always the HOMO/LUMO Transition

The ability to tune excited-state energies is crucial to many areas of molecular design. In many cases, this is done based on the energies of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO). However, this viewpoint is incomplete neglecting the many-body nature of the underlying excited-state wave functions. Within this work, we highlight the importance of two crucial terms, other than orbital energies, that contribute to the excitation energies and show how to quantify them from quantum chemistry computations: a Coulomb attraction and a repulsive exchange interaction. Using this framework, we explain under which circumstances the lowest excited state of a molecule, of either singlet or triplet multiplicity, is not accessed via the HOMO/LUMO transition and show two paradigmatic examples. In the case of the push-pull molecule ACRFLCN, we highlight how the lowest triplet excited state is a locally excited state lying below the HOMO/LUMO charge transfer state due to enhanced Coulomb binding. In the case of the naphthalene molecule, we highlight how the HOMO/LUMO transition (the 1La state) becomes the second excited singlet state due to its enhanced exchange repulsion term. More generally, we explain why excitation energies do not always behave like orbital energy gaps, providing insight into photophysical processes as well as methodogical challenges in describing them.

Application of the reference interaction site model self-consistent field method based on the Dirac-Hartree–Fock wave function to a chemical reaction

The reference interaction site model self-consistent field (RISM-SCF) method is a combined method of the electronic structure theory of molecules and the integral equation theory of molecular liquids. The RISM-SCF method based on the Dirac-Hartree-Fock wave function, recently proposed, is applied to a chemical reaction, specifically, a Menshutkin reaction in aqueous solution. The Helmholtz energy profile along the reaction coordinate is calculated and the characteristics of the reaction are discussed based on energy component analysis.

Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors.

Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of -10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤-8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of -61.42 kcal/mol and -61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = -53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease.

Effect of alanine versus serine at position 88 of human transthyretin mutants on the protein stability.

Human transthyretin (TTR) is a homo-tetrameric plasma protein associated with a high percentage of β-sheet forming amyloid fibrils. It accumulates in tissues or extracellular matrices to cause amyloid diseases. Free energy simulations with thermodynamic integration based on all-atom molecular dynamics simulations have been carried out to analyze the effects of the His88→Ala and Ser mutations on the stability of human TTR. The calculated free energy change differences (ΔΔG) caused by the His88→Ala and His88→Ser mutations are -1.84±0.86 and 7.56±0.55kcal/mol, respectively, which are in excellent agreement with prior reported experimental values. The simulation results show that the H88A mutant is more stable than the wild type, whereas the H88S mutant is less stable than the wild type. The free energy component analysis shows that the contribution to the free energy change difference (ΔΔG) for the His88→Ala and His88→Ser mutations mainly arise from electrostatic and van der Waals interactions, respectively. The electrostatic term stabilizes the H88A mutant more than the wild type, but the van der Waals interaction destabilizes the H88S mutant relative to the wild type. Individual residue contributions to the free energy change show neighboring residues exert stabilizing and destabilizing influence on the mutants. The implications of the simulation results for understanding the stabilizing and destabilizing effect and its contribution to protein stability are discussed.

Exploring actinomycetes natural products to identify potential multi-target inhibitors against Leishmania donovani.

Visceral leishmaniasis (VL) is a neglected tropical disease that mainly affects the poor population of the Indian, African, and South American subcontinent. The increasing resistance to antimonial and miltefosine and frequent toxicity of amphotericin B drives an urgent need to develop an anti-leishmanial drug with excellent efficacy and safety profile. In this study, three sequential docking protocols (HTVS, SP, and XP) were performed to screen the secondary metabolites (n = 6519) from the actinomycetes source against five key proteins involved in the metabolic pathway of Leishmania donovani. Those proteins were adenine phosphoribosyltransferase (PDB ID: 1QB7), trypanothione reductase (PDB ID: 2JK6), N-myristoyl transferase (PDB ID: 2WUU), pteridine reductase (PDB ID: 2XOX), and MAP kinase (PDB ID: 4QNY). Although the binding energy of top ligands was predicted using the MM-GBSA module of the Schrödinger suite. SP and XP docking mode resulted in 55 multi-targeted ligands against L donovani. MM-GBSA analysis selected the top 18 ligands with good-binding affinity and the binding-free energy for four proteins, as mentioned earlier, when compared with the miltefosine, paromomycin, and a reference ligand selected for each target. Finally, molecular dynamics simulation, post-MD-binding-free energy (MM-PBSA), and principal component analysis (PCA) proposed three best ligands (Adenosine pentaphosphate, Atetra P, and GDP-4-keto-6-deoxymannose) qualifying the above screening parameters and confirmed as a potential drug candidate to fight against Leishmania donovani parasites.

Molecular Basis of Inhibitory Mechanism of Naltrexone and Its Metabolites through Structural and Energetic Analyses.

Naltrexone is a potent opioid antagonist with good blood–brain barrier permeability, targeting different endogenous opioid receptors, particularly the mu-opioid receptor (MOR). Therefore, it represents a promising candidate for drug development against drug addiction. However, the details of the molecular interactions of naltrexone and its derivatives with MOR are not fully understood, hindering ligand-based drug discovery. In the present study, taking advantage of the high-resolution X-ray crystal structure of the murine MOR (mMOR), we constructed a homology model of the human MOR (hMOR). A solvated phospholipid bilayer was built around the hMOR and submitted to microsecond (µs) molecular dynamics (MD) simulations to obtain an optimized hMOR model. Naltrexone and its derivatives were docked into the optimized hMOR model and submitted to µs MD simulations in an aqueous membrane system. The MD simulation results were submitted to the molecular mechanics–generalized Born surface area (MMGBSA) binding free energy calculations and principal component analysis. Our results revealed that naltrexone and its derivatives showed differences in protein–ligand interactions; however, they shared contacts with residues at TM2, TM3, H6, and TM7. The binding free energy and principal component analysis revealed the structural and energetic effects responsible for the higher potency of naltrexone compared to its derivatives.

Modulation of human transthyretin stability by the mutations at histidine 88 studied by free energy simulation.

Human transthyretin (TTR) is a homotetrameric plasma protein associated with a high percentage of β-sheet, which forms amyloid fibrils and accumulates in tissues or extracellular matrix to cause amyloid diseases. Free energy simulations based on all-atom molecular dynamics simulations were carried out to analyze the effects of the His88 → Arg, Phe, and Tyr mutations on the stability of human TTR. The calculated free energy change differences (ΔΔG) caused by the His → Arg, Phe, and Tyr mutations at position 88 are 6.48 ± 0.45, -9.99 ± 0.54, and 2.66 ± 0.33 kcal/mol, respectively. These calculated free energy change differences between wild type and the mutants are in excellent agreement with prior experimental values. Our simulation results show that the wild type of the TTR is more stable than H88R and H88Y mutants, whereas it is less stable than the H88F mutant. The free energy component analysis shows that the primary contribution to the free energy change difference (ΔΔG) for the His → Arg mutation arises from electrostatic interaction; the ΔΔG for the His → Phe mutation is from van der Waals and electrostatic interactions and that for the His → Tyr mutation from covalent interaction. The simulation results show that the free energy calculation with thermodynamic integration is beneficial for understanding the detailed microscopic mechanism of protein stability. The implications of the results for understanding stabilizing and destabilizing effect of the mutation and the contribution to protein stability are discussed.

Origin of the unexpected attractive interactions between positive σ-holes and positive π-lumps

The unexpected attractive interactions between positive σ-holes and positive π-lumps in the complexes formed by 2,3,4,5-tetrafluorothiophene (C4F4S) and 2,3,4,5-tetrafluoroselenophene (C4F4Se) with Br2, BrCl, BrF, Cl2 and ClF, respectively, have been investigated by quantum chemical calculations. All the structures bound by these counter-intuitive noncovalent interactions (CI-NCIs) are real minima on the potential energy surfaces. The interaction energy of the complex C4F4Se···BrF reaches −5.49 kcal/mol. Energy component analysis reveals that, at the equilibrium intermolecular distances, these CI-NCIs are electrostatically attractive not electrostatically repulsive as expected. It is the short-range charge penetration that causes the electrostatically attractive interaction between positive σ-hole and positive π-lump. It is also found that, although the dispersion and electrostatics play a larger role in stabilizing these CI-NCIs, there is also a very large (up to 29%) contribution due to the induction.

Electronic Polarization Is Essential for the Stabilization and Dynamics of Buried Ion Pairs in Staphylococcal Nuclease Mutants.

Buried charged residues play important roles in the modulation of protein stabilities and conformational dynamics and make crucial contributions to protein functions. Considering the generally nonpolar nature of protein interior, a key question concerns the contribution of electronic polarization to the stabilization and properties of buried charges. We answer this question by conducting free energy simulations using the latest polarizable CHARMM force field based on Drude oscillators for a series of Staphylococcal nuclease mutants that involve a buried Glu-Lys pair in different titration states and orientations. While a nonpolarizable model suggests that the ionized form of the buried Glu-Lys pair is more than 40 kcal/mol less stable than the charge-neutral form, the two titration states are comparable in stability when electronic polarization is included explicitly, a result better reconcilable with available experimental data. Analysis of free energy components suggests that additional stabilization of the ionized Glu-Lys pair has contributions from both the enhanced salt-bridge strength and stronger interaction between the ion-pair and surrounding protein residues and penetrated water. Despite the stronger direct interaction between Glu and Lys, the ion-pair exhibits considerably larger and faster structural fluctuations when polarization is included, due to compensation of interactions in the cavity. Collectively, observations from this work provide compelling evidence that electronic polarization is essential to the stability, hydration, dynamics, and therefore function of buried charges in proteins. Therefore, our study advocates for the explicit consideration of electronic polarization for mechanistic and engineering studies that implicate buried charged residues, such as enzymes and ion transporters.

Coacervation of poly-electrolytes in the presence of lipid bilayers: mutual alteration of structure and morphology.

Many intrinsically disordered peptides have been shown to undergo liquid–liquid phase separation and form complex coacervates, which play various regulatory roles in the cell. Recent experimental studies found that such phase separation processes may also occur at the lipid membrane surface and help organize biomolecules during signaling events; in some cases, phase separation of proteins at the membrane surface was also observed to lead to significant remodeling of the membrane morphology. The molecular mechanisms that govern the interactions between complex coacervates and lipid membranes and the impacts of such interactions on their structure and morphology, however, remain unclear. Here we study the coacervation of poly-glutamate (E30) and poly-lysine (K30) in the presence of lipid bilayers of different compositions. We carry out explicit-solvent coarse-grained molecular dynamics simulations by using the MARTINI (v3.0) force-field. We find that more than 20% anionic lipids are required for the coacervate to form stable contact with the bilayer. Upon wetting, the coacervate induces negative curvature to the bilayer and facilitates local lipid demixing, without any peptide insertion. The magnitude of negative curvature, extent of lipid demixing, and asphericity of the coacervate increase with the concentration of anionic lipids. Overall, we observe a decrease in the number of contacts among the polyelectrolytes as the droplet spreads over the bilayer. Therefore, unlike previous suggestions, interactions among polyelectrolytes do not constitute a driving force for the membrane bending upon wetting by the coacervate. Rather, analysis of interaction energy components suggests that bending of the membrane is favored by enhanced interactions between polyelectrolytes with lipids as well as with counterions. Kinetic studies reveal that, at the studied polyelectrolyte concentrations, the coacervate formation precedes bilayer wetting.

Microstructure evolution and wettability regulation of air-exposed hydrogen-free diamond-like carbon films

Regulation of surface wettability is of vital significance to diamond-like carbon (DLC) serving as multi-functional coatings in many important fields. In this study, hydrogen-free DLC films with highly adjustable surface wettability induced by surface local hybridized structures were deposited on silicon substrates by RF magnetron sputtering under different substrate temperatures and RF powers. A non-monotonic dependency of surface wettability on the hybridization states, which is just inverse for polar and non-polar liquids, was found on the homogeneous DLC films with nanoscale surface roughness. In particular, the wetting transition from hydrophilicity to hydrophobicity occurred on the DLC films in contact with water. A clear picture about the essential correlation of surface wettability to microstructures of DLC films was drawn in terms of detailed analysis of surface energy components associated with the evolution of sp2-C bonds or clusters in content, type and distortion. Further, a possible mechanism accounting for the wetting transition of the DLC films was also proposed. This work aims to reveal the wetting nature of hydrogen-free DLC films versus graphite and diamond, and provide an available strategy to fabricate high-performance DLC films with special surface wettability used in aqueous environment.

The role of 4D flow MRI for clinical applications in cardiovascular disease: current status and future perspectives.

Magnetic resonance imaging (MRI) four-dimensional (4D) flow is a type of phase-contrast (PC) MRI that uses blood flow encoded in 3 directions, which is resolved relative to 3 spatial and temporal dimensions of cardiac circulation. It can be used to simultaneously quantify and visualize hemodynamics or morphology disorders. 4D flow MRI is more comprehensive and accurate than two-dimensional (2D) PC MRI and echocardiography. 4D flow MRI provides numerous hemodynamic parameters that are not limited to the basic 2D parameters, including wall shear stress (WSS), pulse wave velocity (PWV), kinetic energy, turbulent kinetic energy (TKE), pressure gradient, and flow component analysis. 4D flow MRI is widely used to image many parts of the body, such as the neck, brain, and liver, and has a wide application spectrum to cardiac diseases and large vessels. This present review aims to summarize the hemodynamic parameters of 4D flow MRI technology and generalize their usefulness in clinical practice in relation to the cardiovascular system. In addition, we note the improvements that have been made to 4D flow MRI with the application of new technologies. The application of new technologies can improve the speed of 4D flow, which would benefit clinical applications.

The Face-to-Face σ-Hole⋯σ-Hole Stacking Interactions: Structures, Energies, and Nature

The existence of the π⋯π stacking interaction is well-known. Similarly, it is reasonable to assume the existence of the σ-hole⋯σ-hole stacking interaction. In this work, the structures, energies, and nature of the face-to-face σ-hole⋯σ-hole stacking interactions in the crystal structures have been investigated in detail by the quantum chemical calculations. The calculated results clearly show that the face-to-face σ-hole⋯σ-hole stacking interactions exist and have unique properties, although their strengths are not very significant. The energy component analysis reveals that, unlike many other dispersion-dominated noncovalent interactions in which the induction energies always play minor roles for their stabilities, for the face-to-face σ-hole⋯σ-hole stacking interaction the contribution of the induction energy to the total attractive energy is close to or even larger than that of the electrostatic energy. The structures, energies, and nature of the face-to-face σ-hole⋯σ-hole stacking interactions confined in small spaces have also been theoretically simulated. One of the important findings is that encapsulation of the complex bound by the face-to-face σ-hole⋯σ-hole stacking interaction can tune the electronic properties of the container.

Energy Component Analysis of Electric Field-Induced Shape Change in Water Nanodroplets

We present a comprehensive classical molecular dynamics study of water nanodroplets under the influence of an externally applied electric field. Our simulations cover a wide range of droplet sizes and electric field strengths, which allows for a thorough exploration of the structural and energetic behavior of nanodroplets in the presence of an external electric field. Our analysis reveals the molecular-level mechanism behind the shape extension of a nanodroplet from a spheroid to a highly prolate ellipsoid as the propensity of the water dipoles to align with the electric field while simultaneously restructuring to minimize the dipole–dipole interaction energy. We also develop a quantitative theory that describes the energetic landscape for the nanodroplet shape extension process and allows predictions of the nanodroplet behavior based on its initial size and the strength of the applied field.

Elucidating the Electronic Structure of a Delayed Fluorescence Emitter via Orbital Interactions, Excitation Energy Components, Charge-Transfer Numbers, and Vibrational Reorganization Energies.

Recently, Wang and co-workers carried out frontier molecule orbital engineering in the design of m-Cz-BNCz, a thermally activated delayed fluorescence (TADF) molecule that emits pure green light at an external quantum efficiency of 27%. To further understand the underlying molecular design principles, we employed four advanced electronic structure analysis tools. First, an absolutely localized molecular orbitals (ALMO-) based analysis indicates an antibonding combination between the highest occupied molecular orbitals (HOMOs) of the donor 3,6-di-tert-butylcarbazole fragment and the acceptor BNCz fragment, which raises the HOMO energy and red-shifts the fluorescence emission wavelength. Second, excitation energy component analysis reveals that the S1-T1 gap is dominated by two-electron components of the excitation energies. Third, charge transfer number analysis, which is extended to use fragment-based Hirshfeld weights, indicates that the S1 and T1 excited states of m-Cz-BNCz (within time-dependent density functional theory) have notable charge transfer characters (27% for S1 and 12% for T1). This provides a balance between a small single-triplet gap and a substantial fluorescence intensity. Last, a vibrational reorganization energy analysis pinpoints the torsional motion between the BNCz and Cz moieties of m-Cz-BNCz as the source for its wider emission peak than that of p-Cz-BNCz. These four types of analyses are expected to be very valuable in the study and design of other TADF and functional dye molecules.

ACE-2-Derived Biomimetic Peptides for the Inhibition of Spike Protein of SARS-CoV-2.

SARS-CoV-2, a novel coronavirus causing overwhelming death and infection worldwide, has emerged as a pandemic. Compared to its predecessor SARS-CoV, SARS-CoV-2 is more infective for being highly contagious and exhibiting tighter binding with host angiotensin-converting enzyme 2 (hACE-2). The entry of the virus into host cells is mediated by the interaction of its spike protein with hACE-2. Thus, a peptide that has a resemblance to hACE-2 but can overpower the spike protein–hACE-2 interaction will be a potential therapeutic to contain this virus. The non-interacting residues in the receptor-binding domain of hACE-2 have been mutated to generate a library of 136 new peptides. Out of this library, docking and virtual screening discover seven peptides that can exert a stronger interaction with the spike protein than hACE-2. A peptide derived from simultaneous mutation of all the non-interacting residues of hACE-2 yields almost three-fold stronger interaction than hACE-2 and thus turns out here to be the best peptide inhibitor of the novel coronavirus. The binding of the best peptide inhibitor with the spike protein is explored further by molecular dynamics, free energy, and principal component analysis, which demonstrate its efficacy compared to hACE-2. The delivery of the screened inhibitors with nanocarriers like metal–organic frameworks will be worthy of further consideration to boost their efficacy.

Theoretical model of maximum spreading diameter on superhydrophilic surfaces

Liquid droplets impacting on the solid surface is an ubiquitous phenomenon in natural, agricultural, and industrial processes. The maximum spreading diameter of a liquid droplet impacting on a solid surface is a significant parameter in the industrial applications such as inkjet printing, spray coating, and spray cooling. However, former models cannot accurately predict the maximum spreading diameter on a superhydrophilic surface, especially under low Weber number (<i>We</i>). In this work, the spreading characteristics of a water droplet impacting on a superhydrophilic surface are explored by high-speed technique. The spherical cap of the spreading droplet, gravitational potential energy, and auxiliary dissipation are introduced into the modified theoretical model based on the energy balance. The model includes two viscous dissipation terms: the viscous dissipation of the initial kinetic energy and the auxiliary dissipation in spontaneous spreading. The energy component analysis in the spreading process shows that the kinetic energy, surface energy, and gravitational potential energy are all transformed into the viscous dissipation on the superhydrophilic surface. The transformation of surface energy into viscous dissipation is dominant at lower <i>We</i> while the transformation of kinetic energy into viscous dissipation is dominant at higher <i>We</i>. It is found that the gravitational potential energy and auxiliary dissipation play a significant role in spreading performance at low <i>We</i> according to the energy component analysis. Moreover, the energy components predicted by the modified model accord well with the experimental data. As a result, the proposed model can predict the maximum spreading diameter of a droplet impacting on the superhydrophilic surface accurately. Furthermore, the model proposed in this work can predict the maximum spreading diameter of the droplet impacting on the hydrophilic surface and hydrophobic surface. The results of this work are of great significance for controlling droplet spreading diameter in spray cooling and falling film evaporation.

The σ-hole⋯σ-hole stacking interaction: An unrecognized type of noncovalent interaction.

The σ-hole⋯σ-hole stacking interaction, an unrecognized type of noncovalent interaction, has been found to be present in large quantities in the Cambridge Structural Database. In the σ-hole⋯σ-hole stacking interaction, each of the two interacting σ-holes has the dual electron donor/electron acceptor character; when one σ-hole acts as an electron donor, the other σ-hole acts as an electron acceptor, and vice versa. The σ-hole⋯σ-hole stacking interaction is clearly different from the σ-hole bond in which the charge transfer occurs mainly from the electron donor to the σ-hole. Energy component analysis shows that the σ-hole⋯σ-hole stacking interaction is dominated by the dispersion energy, which is similar to the nature of the aromatic stacking interaction between unsaturated molecules or the σ⋯σ stacking interaction between saturated molecules.

Structural and binding insights into HIV-1 protease and P2-ligand interactions through molecular dynamics simulations, binding free energy and principal component analysis

HIV-1 protease (HIV-1-pr) plays an important role in viral replication and maturation, making it one of the most attractive targets for anti-retroviral therapy. To design new effective inhibitors able to combat drug resistance in mutant HIV-1-pr variants, it is essential to gain further understanding about the mechanisms by which the recently proposed inhibitors deactivate the mutant HIV-1-pr variants. In the present work, we explored the interactions between two P2-ligands (DRV, and one new derivative, 4UY) with wild type (WT) and two multiple mutant HIV-1-pr variants (p20 and p51) with all atom molecular dynamics (MD) simulations, binding free energy calculations, and principal component analysis (PCA). The trajectories of MD simulations show that both 4UY and DRV primarily bind with the active sites, flap and 80s loop regions of HIV-1-pr variants through either hydrogen bonds or hydrophobic interactions. More hydrogen bonds and hydrophobic interactions were located for 4UY/HIV-1-pr complexes than for DRV/HIV-1-pr counterparts. More importantly, 4UY was found to have an extra hydrogen bond with the backbone of Gly48’ in the flap region of the HIV-1-prs. The flap tip-tip distance (I50–I50’) and flap tip-active site distance (I50-D25 and I50′-D25’) indicate that the flaps turn more closed in 4UY bound HIV-1-prs than DRV bound ones, and the former also have more compact hydrophobic cavities than the latter. Further, the vector projections from PCA indicate that 4UY/DRV inhibitor binding projects the closing of flap in HIV-1-pr variants. In line with the above trajectory analysis, the thermodynamics calculation with MM-PBSA method suggests much stronger binding affinity for 4UY/HIV-1-pr than DRV/HIV-1-pr by 4.3–6.4 kcal/mol. Although p20 and p51 also induce weaker binding due to multiple mutants for 4UY inhibitor by 1.9–1.8 kcal/mol, their bindings to the new P2 ligand (4UY) are indeed significantly enhanced as compared to DRV. The thermodynamic components responsible for the binding differences and the contribution from key residues to the binding were also discussed in detail.

Analysis of energy and major components in chromatographic signals for the diagnosis of prostate cancer

The prostate exam is an early detection tool to prevent prostate cancer and the main diagnostic tools for obtaining signs are generally invasive. This article tries chromatographic signals from the urine of prostate cancer patients and control patients as a non-invasive examination proposal. For this purpose, methodologically, urine samples are taken, digitized in chromatograms, treated with mathematical techniques and classified. The mathematical techniques are time normalization, dead time elimination, baseline correction, noise elimination, and peak alignment. Classification techniques analyze energy, in the domain of time and frequency, and the main components in sedimentation graphs and scores. As a result, the chromatographic signal is characterized and identifies the characteristic curve that represents the signal of prostate cancer patients and control patients. The data structure shows a cluster distribution of 88.88% of the vectors for the control patients. In the case of prostate cancer patients, the distribution of data is in clusters around the area defined by control patients. This characterization demarcates signal classification regions to diagnose possible prostate cancer patients, validating the relationship between the chromatographic signal and cancer.