COMPUTATIONAL
METHOD FOR DRUG
EFFECTIVENESS
ANALYSIS
ENISEMO OMOLOLA ABIGEAL
INTRODUCTION
• Nowadays, most point-of-care healthcare systems consist of several biomedical
sensors to acquire physiological signals and data to support health condition
monitoring and early-stage pathology screening functions. Integration and
fusion of the massive multiscale biomedical signals recorded by wearable
sensors or medical images generated by multiple imaging modalities have
attracted more and more attentions from the research community. Advanced
computational tools can be effectively used to compute signal dynamics, time
frequency properties, data correlations, and statistical parameters for
understanding the complex physiological processes associated with disease
symptoms. The emerging deep learning neural networks and machine learning
algorithms have the advantages of representing high-dimensional data features
with hierarchical network layers, and achieving the accurate pattern
classification results, which helps provide the informative diagnostic references
COMPUTATIONAL SCIENCE
• Computational techniques are fast, easier, reliable and efficient way or
method for solving mathematical, scientific, engineering, geometrical,
geographical and statistical problems via the aid of computers.
• The step-wise procedure may entail the use of iterative, looping,
stereotyped or modified processes which are incomparably less
stressful than solving problems-manually.
MASS SPECTROMETRY IMAGING (MSI)
• Mass spectrometry imaging (MSI) is a powerful label-free technique
that enables simultaneous imaging of hundreds of molecules in
biological samples with high sensitivity and unprecedented molecular
specificity.
• Many classes of biomolecules including metabolites, lipids, peptides,
proteins, and drugs have been characterized using MSI. In the past four
decades, MSI technologies underwent impressive developments
through continuous advances in both soft ionization techniques and
mass spectrometry (MS) instrumentation.
SURFACE ENHANCED RAMAN SPECTROSCOPY
FOR BACTERIAL PATHOGEN IDENTIFICATIONS
• In clinical medicine, understanding biological processes is critical for
conducting early detection and identifying hidden disorders, as well as
commencing effective treatments. Furthermore, precise and reliable
metabolite analysis is required to get a better knowledge of biological
processes or to assess therapeutic efficacy. Pathogenic bacteria continue to be
a major public health concern, causing an estimated 550 million infections and
5.2 million deaths each year.
• To help protect the human population from infectious diseases, rapid detection
and efficient identification of pathogens are critically required. In-vitro approach
• The detection of bacteria and other pathogens at an initial and sensitive stage
is important for infectious disease diagnosis and the prevention of epidemics
and outbreaks of disease threats.
BIOMOLECULAR SIMULATIONS IN DRUG
SCREENING AND DESIGN
• IDepending on the biological problems to be studied, multiscale models
will be used in biomolecular simulations. The combination of quantum
mechanics (QM) and molecular mechanics (MM) (QM/MM) can be used to
study the electronic properties, simulate chemical reactions (e.g., the
enzyme catalysis mechanism), and calculate spectra in a single simulation,
which can be used to elucidate the action mechanism of certain drugs.
• Another widely used biomolecular method is molecular dynamics (MD)
simulation, which applies empirical molecular mechanics (MM) force fields
and is based on classical Newtonian mechanics.
DRUG DESIGN AND VIRTUAL SCREENING
• The design, discovery, and development of drugs are complex
processes involving many different fields of knowledge and are
considered a time-consuming and laborious inter-disciplinary work.
Different drug design methods and virtual screening will be very useful
to design and find rational drug molecules based on the target
macromolecule that interacts with the drug and thus speed up the
whole drug discovery process (Xubo et al., 2020).
MOLECULAR DOCKING
• IMolecular docking, which predicts interaction patterns between proteins
and small molecules as well as proteins and proteins, to evaluate the
binding between two molecules, is widely used in the field of drug
screening and design.
• The theoretical basis is that the process of ligand and receptor recognition
relies on spatial shape matching and energy matching, which is the
theory of “inducing fit”. Determining the correct binding conformation of
small molecule ligands and protein receptors in the formation of complex
structures is the basis for drug design and studying its action mechanism.
PHARMACOPHORE MODELING
• A pharmacophore is an abstract description of molecular features necessary for
molecular recognition of a ligand by a biological macromolecule, which explains
how structurally diverse ligands can bind to a common receptor site.
• When a drug molecule interacts with a target macromolecule, it produces a
geometrically and energetically matched active conformation with the target.
Medicinal chemists found that different chemical groups in drug molecules have
different effects on activity, and changes to some groups have a great influence
on the interaction between drugs and targets, while others have little effect.
Moreover, it was found that molecules with the same activity tend to have some
of the same characteristics.
MOLECULAR DYNAMICS OF CARDIAC
MODELLING
• Multiscale modeling of the drugs in an excitable system is critical
because experiments on a single system scale cannot reveal the
underlying effects of multiple drug interactions. A computationally
based approach to predict the emergency effects of drugs on excitatory
rhythms may form an interactive technology-driven process for the
drug and disease screening industry, research and development
academia, and patient-oriented medical clinic. There are potentially far-
reaching implications because millions of people affected by
arrhythmia each year will benefit from improved risk stratification of
drug-based interventions.
INTEGRATIVE ANALYSIS OF GENOMICS
AND PHARMACOLOGICAL DATA
• Inspired by the NCI-60 project, several collaborative efforts scaled up
the number of cancer cell lines investigated in pharmacogenomics
studies from the original 60 to more than 1,400, planning to reach over
10,000 publicly available cancer models in the near future. The
massive amount of genomic and drug response data generated by
these screenings are commonly collected in databases that, through
dedicated web portals, provide direct insights into potential interactions
between the analyzed cancer cell lines and the tested drugs.
SUMMARY AND CONCLUSION
• Summary
• In summary, computational methods have revolutionized drug effectiveness analysis,
providing powerful tools for extracting insights, identifying patterns, and making
informed decisions. By utilizing these methods, researchers and practitioners can:
• Conclusion
• The combined use of in vitro, in vivo, and in silico methods has revolutionized drug discovery. In vitro
approaches provide controlled environments for initial evaluations, while in vivo studies offer
comprehensive insights into physiological interactions. Meanwhile, in silico methods expedite the
discovery process with computational predictions.
