Contact Information
Prof. Dr. Andrzej Bąk
Email: andrzej.bak@akademiaslaska.edu.pl, andrzej.bak@us.edu.pl
Phone: 32 359 11 97
Office: Szkolna 9 Street, Katowice, office number 40, I floor
Introduction to Medical Informatics and Biostatistics
Fields:
The discipline focuses on the integration of data, informatics, and knowledge to enhance medical practices and streamline patient care. This encompasses various aspects, including health information systems, data management, and the use of technology in diagnostics and treatment.
It entails an in-depth study of coding drug structures using specialized software and molecular editors, allowing for the creation of extensive and detailed databases of pharmaceuticals, which are crucial for research and development.
The exploration of the role of receptors as critical molecular targets in therapeutics dives into how they mediate drug effects at the cellular level, impacting the efficacy and safety of treatments.
A comprehensive analysis of molecular descriptors is essential, emphasizing lipophilicity and its significant impact on drug absorption, distribution, metabolism, and overall therapeutic effectiveness.
Techniques:
Computer-Assisted Molecular Design (CAMD): This employs computational methods, including molecular modeling and simulations, enabling researchers to design and optimize drug candidates effectively while predicting their behavior in biological systems.
Quantitative Structure-Activity Relationship (QSAR) modeling: A sophisticated mathematical approach utilized to correlate chemical structure with biological activity, greatly aiding in the prediction of the efficacy of new compounds and their potential as therapeutic agents.
Artificial Intelligence (AI) and Neural Networks (NN) in medicine: The harnessing of AI algorithms to analyze extensive datasets can identify patterns in disease diagnosis and treatment effectiveness, facilitating personalized medicine and improving clinical outcomes.
Biostatistics Basics:
Fundamental techniques in data preprocessing ensure the cleaning and preparation of datasets for rigorous analysis, fostering reliable results in medical research.
Basic data modeling procedures establish statistical relationships and validate hypotheses, essential in clinical trials and epidemiological studies.
Data visualization techniques, including the use of advanced software tools, facilitate the representation of complex data visually, aiding in better interpretation and insight into research findings.
An overview of in-silico medicine introduces computer simulation and modeling's critical role in supporting clinical decision-making, highlighting its growing relevance in personalized therapies.
Protein Chemistry - Historical Overview
Historical Milestones:
1816: F. Magendi identified proteins as essential nutrients in the human diet, laying the groundwork for nutritional science and leading to further advancements in dietary studies.
1839: G.J. Mulder coin the term "protein," derived from the Greek word "proteios," meaning primary or of first importance, emphasizing their fundamental role in biology and health.
Pioneering work by researchers such as W. Kuhne, F. Hoffmeister, A. Kossel, and A. Danilewski has greatly advanced the understanding of amino acids as the building blocks of proteins, leading to breakthroughs in biochemistry.
E. Fischer's Contributions: His groundbreaking research into synthetic peptides has significantly advanced the field of protein synthesis and structure elucidation, pushing the boundaries of biochemical and pharmaceutical sciences.
Protein Structure
Overview:
Proteins are linear polymers constructed from 20 different amino acids. The specific sequence of these amino acids (the primary structure) is crucial as it determines the protein's unique structure and functionality.
Classification of Peptides:
Dipeptides: Consist of 2 amino acids linked by a peptide bond.
Oligopeptides: Chains containing up to 10 amino acids, often exhibiting unique biological properties.
Polypeptides: Longer chains comprising more than 10 amino acids; they can fold into functional proteins.
Proteins: Complex structures consisting of approximately 100 amino acids or more, often functioning as biological catalysts or structural components, fundamental to cellular functions.
Functions of Proteins:
Structural Proteins: Examples include keratin and collagen, providing support and shape to cells and tissues, critical for structural integrity.
Hormonal Proteins: Regulatory proteins like insulin help maintain homeostasis by controlling physiological processes.
Enzymatic Proteins: Catalysts like DNA polymerase facilitate essential biochemical reactions, including DNA replication and repair, playing a pivotal role in cellular function.
Amino Acid Structure
Natural Amino Acids:
A total of 20 distinct natural amino acids function as bifunctional compounds, each uniquely characterized by a general structure comprising an amino group (-NH2) and a carboxyl group (-COOH), essential for their biochemical roles.
For scientific communication, each amino acid is represented by both three-letter and single-letter symbols, aiding in notation and analysis across research fields.
Peptide Bonds
Formation of Peptide Bonds:
Peptide bonds, or amide bonds, link amino acids into peptides through a dehydration synthesis reaction, during which a molecule of water is released, forming the backbone of protein structures.
The formation of peptide bonds occurs through the interaction of the α-carboxyl and α-amino groups of adjacent amino acids, a critical step in the synthesis of peptides and proteins crucial for all biological systems.
Spatial Structures of Proteins
Primary Structure:
Defined as the linear sequence of amino acids, which is determined by the genetic code, influencing all subsequent structural levels and protein function. For example, the specific amino acid sequence of insulin is critical for its regulatory role in glucose metabolism.
Secondary Structure:
Local structural formations arise from the angles between peptide bonds, leading to the development of folding patterns such as alpha-helices and beta-sheets, which are stabilized by hydrogen bonds, contributing to the protein's overall stability.
Tertiary Structure:
The overall three-dimensional conformation of a protein is shaped by interactions among side chain groups (e.g., hydrophobic interactions, ionic bonds), determining its functional capability and biological activity.
Quaternary Structure:
Complex structures involving multiple polypeptide chains functioning together, forming dimers (two), trimers (three), or larger assemblies, essential for biological function and activity.
Protein Classification by Function
Enzymes: Catalytic proteins such as pepsin, facilitating biochemical reactions, crucial for metabolic pathways including digestion.
Hormones: Regulatory proteins like insulin that control various physiological processes and maintain homeostasis within the body.
Storage Proteins: Nutrient reservoirs such as ferritin, which store minerals like iron, crucial for various biological functions.
Structural Proteins: Provide essential support and shape to tissues, for example, collagen in connective tissues.
Transport Proteins: Involved in the transportation of essential molecules, such as hemoglobin, which transports oxygen in the bloodstream.
Protective Proteins: Defense mechanisms such as antibodies that protect the body against pathogens and infections, crucial for the immune response.
Molecular Descriptors and Properties
Molecular Descriptors (S): These value metrics, calculated from drug molecules using computational methods, assist in understanding a drug's potential behavior and interactions during biological processes.
Properties (P): Derived from laboratory measurements of actual drug molecules, these empirical data are critical for determining therapeutic effects and drug efficacy.
Lipophilicity: A critical parameter in pharmacokinetics; the quantitative descriptor logP represents the solute concentration ratio in a two-phase system (n-octanol/water), influencing a drug's capacity to cross biological membranes and permeate various tissues, affecting the efficacy of therapy.
Various techniques for assessing lipophilicity include the shake-flask method, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC), each providing insights into drug behavior.
Ionization in Medicinal Chemistry
Ionization of Drugs: Approximately 85% of pharmaceutical compounds are ionizable, significantly affecting their solubility and distribution in biological systems.
The degree of ionization can substantially influence pharmacokinetic properties, encompassing Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiles, crucial for drug development and patient safety.
pH Influence: The pH level of various bodily compartments (such as the stomach and blood) directly affects the ionization state of drugs, subsequently impacting their therapeutic efficacy, safety, and overall pharmacological activity.
Lipinski Rule of Five
Assessing Drug-Like Characteristics: Lipinski's rule serves as a guideline for predicting the oral bioavailability of drug candidates. It emphasizes the importance of specific physicochemical properties that can influence drug absorption and therapeutic effectiveness.
Rule Summary: No more than one of the following characteristics should be violated:
Molecular weight (MW) ≤ 500
LogP ≤ 5
H-bond donors ≤ 5
H-bond acceptors ≤ 10
Greater adherence to these principles generally increases the likelihood of enhanced bioavailability and therapeutic success in drug development, guiding researchers in the design of effective pharmaceuticals.
Conclusion
A comprehensive understanding of the complex interplay between molecular descriptors, protein structures, and drug properties is vital for advancing drug development processes and enhancing therapeutic outcomes in medicinal chemistry, ultimately improving the efficacy and safety of therapeutic interventions.