Doctoral student in Computational Chemistry

Subject description

Research in computational chemistry entails the development and application of quantum mechanical and statistical mechanical methods to describe chemical systems and processes. These methods are applied to solve or illuminate questions within biochemistry, medicinal chemistry, physical chemistry and intermolecular interaction.

Work duties

Calculating accurate estimates for the binding affinity of small molecules (e.g. drug candidates) to a macromolecular receptor (e.g. a protein) is one of the most important challenges of computational chemistry. The most promising approach is free energy perturbation (FEP), which normally gives a useful accuracy for pharmacy industry. However, for certain targets, the accuracy is much worse. In particular, metalloproteins, in which the drug candidate binds to the metal, provide a prominent problem for pharmaceutical applications. In this project, we will try to solve this problem with a hierarchy of computational approaches. First, we will develop and test two approaches to obtain a bonded molecular mechanics force field for metal sites based on quantum mechanical (QM) calculations. Second, we employ explicit combined QM and molecular mechanics (QM/MM) FEP simulations with different QM methods. Third, we employ data from the latter simulations to develop a machine learning force fields for metal sites that will be used for FEP calculations. We will apply the methods on metalloenzymes of central pharmaceutical interest, e.g. methionine aminopeptidase-2 and matrix metalloproteinase 12. The project is a tight collaboration between Lund University, Chalmers and AstraZeneca.

The main duties of doctoral students are to devote themselves to their research studies which includes participating in research projects and third cycle courses. The work duties can also include teaching and other departmental duties (no more than 20%).

Admission requirements

A person meets the general admission requirements for third cycle courses and study programmes if the applicant:

• has been awarded a second cycle qualification, or
• has satisfied the requirements for courses comprising at least 240 credits of which at least 60 credits were awarded in the second cycle, or
• has acquired substantially equivalent knowledge in some other way in Sweden or abroad.

A person meets the specific admission requirements for third cycle studies in Computational Chemistry if the applicant has:

• At least 120 credits of chemistry courses, of which at least 30 credits from a second cycle degree project within computational chemistry or closely related specialisations. Sixty credits in physics and 60 credits in mathematics also meet the requirements for theoretical chemistry. The specific entry requirement may also have been obtained through other equivalent education.
  
  

Additional requirements:

• Good oral and written proficiency in English.
• Programming skills, as well as experience with Linux and high-performance computing systems.
• Practical experience of computational chemistry methods (quantum chemistry, molecular dynamics, free energy perturbations, etc.).
• Practical experience machine learning.
• Courses in quantum mechanics, statistical mechanics and bioinformatics.

 Assessment criteria

Selection for third cycle studies is based on the student’s potential to profit from such studies. The assessment of potential is made primarily on the basis of academic results from the first and second cycle. Special attention is paid to the following:

1. Knowledge and skills relevant to the thesis project and the subject of study.
2. An assessment of ability to work independently and to formulate and tackle research problems.
3. Written and oral communication skills
4. Other experience relevant to the third cycle studies, e.g. professional experience.

Other assessment criteria:

• Programming skills.
• Experience with Linux and high performance computing systems.
• Practical experience of computational chemistry methods.
• Practical experience machine learning.

Consideration will also be given to good collaborative skills, drive and independence, and how the applicant, through his or her experience and skills, is deemed to have the abilities necessary for successfully completing the third cycle programme.

Terms of employment
Only those admitted to third cycle studies may be appointed to a doctoral studentship. Doctoral studentships are regulated in the Higher Education Ordinance (1993:100), chapter 5, 1-7 §§.

 Instructions on how to apply

Applications shall be written in English and include a cover letter stating the reasons why you are interested in the position and in what way the research project corresponds to your interests and educational background. The application must also contain a CV, degree certificate or equivalent, and other documents you wish to be considered (grade transcripts, contact information for your references, letters of recommendation, etc.).