After today, you should be able to

1.  Understand course structure and expectations.
2.  Outline the requirements and goals of the perspective primers.
3.  Compare and contrast different types of scientific articles.
4.  Explain the key components of the research ecosystem.
5.  Apply effective strategies to find relevant literature.

Meet your teaching team

Instructor
Alex Maldonado, PhD

he/him/his

Postdoctoral Associate in Computational Biology

Alex's fun facts

Every male in my (maternal) family played football 

Alex's fun facts

Part-time jobs

• Construction
• UPS package handler
• Kent County Traffic safety
• Jimmy John's delivery driver
• Wings West ice events

Get to know my ...

Movie taste

Music taste

Tessa the cat

All course material is hosted online

Website: pitt-biosc1630-2024f.oasci.org/

Things that contain student information will be only on Canvas to be FERPA compliant

Assignments will be submitted on Gradescope

Reading and critiquing research

We will be routinely reading primary research articles within computational biology

You will read one research article every two weeks

I have picked several papers across computational biology published in 2023

A pre-class assignment will ensure you are prepared for discussion-based activities

Enhancing your critical thinking by reading literature

"I'm not going to graduate school, so why am I taking a whole class reading literature?"

Problems, solutions, and ideas need to be shared

Every job description likely contains "Excellent communication skills"

We will help you hone your communication skills with writing a perspective paper

You will write a perspective paper during the semester

Writing-intensive courses require 11 to 13 single-spaced pages of writing

This is an atypical two-credit course

I will accept the following graduate fellowship applications in lieu of writing a perspective

• NSF GRFP: Humanities and STEM
• DOE CSGF: High-performance computing
• Hertz Fellowship: Applied STEM

Research statements for these applications are more rigorous than this perspective

After today, you should be able to

1.  Understand course structure and expectations.
2.  Outline the requirements and goals of the perspective primers.
3.  Compare and contrast different types of scientific articles.
4.  Explain the key components of the research ecosystem.
5.  Apply effective strategies to find relevant literature.

Primer 1: Protein structure prediction

AlphaFold has undoubtedly revolutionized protein structure prediction

Primer 1: Protein structure prediction

AlphaFold is a complicated machine learning model that is trained to reproduce experimental structures

It achieves transferability by learning to find coevolutionary signals of residue-residue proximity

Primer 1: Protein structure prediction

Ab initio methods use physical representations and calculations to compute structures

Expensive but interpretable

Should we abandon ab initio methods for protein structure prediction?

Primer 2: Molecular dynamics for drug design

Drug discovery aims to identify drug candidates from a large search space

Primer 2: Molecular dynamics for drug design

Protein-ligand docking can rapidly identify binding poses based on parameterized scoring functions and/or machine learning

Primer 2: Molecular dynamics for drug design

Molecular simulations account for solvent, protein, and ligand dynamics

Significantly enhanced conformational sampling and free energies (e.g., entropy)

Primer 2: Molecular dynamics for drug design

With experimental assays becoming more economical, why spend the time running simulations?

Alchemical simulations systematically turn off the ligand's interaction with proteins

Primer 2: Molecular dynamics for drug design

Experimental techniques probe drug action before investing in clinical trials

Example: Terray Therapeutics

Should we bypass molecular simulations and go straight to experimental assays?

Each primer has no right answer; I'm just looking for your opinion with supporting evidence

After today, you should be able to

1.  Understand course structure and expectations.
2.  Outline the requirements and goals of the perspective primers.
3.  Compare and contrast different types of scientific articles.
4.  Explain the key components of the research ecosystem.
5.  Apply effective strategies to find relevant literature.

Primary literature: Original research by scientists in the field

• Contains novel computational methods, algorithms, or analyses
• Published in peer-reviewed  journals
• Includes detailed methodology, datasets, and statistical analyses
• Often accompanied by open-source code or software tools

Review: Summarizes the current state of knowledge in a specific area

• Synthesis of multiple primary research articles
• No new experimental data presented
• Analyzes trends, gaps, and future directions in research

Perspective: Presents author's viewpoint on a specific topic or issue

After today, you should be able to

1.  Understand course structure and expectations.
2.  Outline the requirements and goals of the perspective primers.
3.  Compare and contrast different types of scientific articles.
4.  Explain the key components of the research ecosystem.
5.  Apply effective strategies to find relevant literature.

Understanding the research ecosystem sheds light on literature caveats

Carnegie classifications of Universitites

Doctorate-granting universities

Hiring tenure-stream professors

Tenure-stream expectations

• Independently publish by year three
• Mentor research trainees
• Invited to speak at institutions and conferences
• Provide service to department and profession
• Develop one undergraduate course

Getting tenure

• Quality, impact, and consistency of research
• Number, size, and prestige of funding sources
• Teaching excellence not required
• Faculty and dean vote; provost has final say

Tenure catalyzes a publish or perish culture

Journal prestige

Impact factor tries to communicate how "groundbreaking" publications in that journal are

Research productivity

H-index is a quick, imperfect way to quantify research quality of a professor

Grant acquisition

• Professors pay (and train) others to do their research
• Provides funding for research projects and lab personnel
• Major Funding Sources:
  • Federal: NIH, NSF, DOE, DOD, NASA
  • Private foundations: Gates Foundation, Howard Hughes Medical Institute
  • Industry partnerships

Obtaining grants is extremely difficult

• Time-consuming application process
• Balancing grant writing with ongoing research and teaching
• Success rates often below 20%
• Navigating changing funding priorities
• Multiple submission rounds

Critical evaluation

Just because it is peer-reviewed does not mean it is perfect

• Do the authors have the appropriate expertise?
• Are the methods state-of-the-art or justified?
• Is the journal reputable?
• Do the results support their conclusions?
• Are the results reproducible?

After today, you should be able to

1.  Understand course structure and expectations.
2.  Outline the requirements and goals of the perspective primers.
3.  Compare and contrast different types of scientific articles.
4.  Explain the key components of the research ecosystem.
5.  Apply effective strategies to find relevant literature.

Literature search activity